Prognosis Of Different Subtypes Research Articles

Longitudinal Assessment of Pulmonary Involvement and Prognosis in Different Subtypes of COVID-19 Patients After One Year Using Low-Dose CT: A Prospective Observational Study.

Severe COVID-19 typically results in pulmonary sequelae. However, current research lacks clarity on the differences in these sequelae among various clinical subtypes. This study aimed to evaluate the changing lung imaging features and predictive factors in patients with COVID-19 pneumonia in northern China over a 12-month follow-up period after the relaxation of COVID-19 restrictions in 2022. Imaging and clinically relevant data from three groups (moderate, severe, and critical) of patients with varying severity were prospectively analyzed. Low-dose CT scans were conducted at 3, 6, and 12 months after discharge, with chest CT images evaluated at baseline and each follow-up using qualitative and quantitative analyses. Clinical symptoms and pulmonary function recovery at 12 months were documented. The correlation between lung function and CT results was analyzed. Univariate and multivariable logistic regression analyses were employed to examine factors influencing prognosis, while a post-hoc analysis model was utilized to investigate the relationships among different groups, time points, and chest CT findings. Among the 103 hospitalized patients with COVID-19 pneumonia, 64 completed the 12-month evaluation. The median age was 63.70 ± 12.15%, and 62.5% (40/64) were men. During the follow-up period, while 67.19% (43/64) showed abnormalities, including fibrotic changes in 9.38% (6/64). Multivariable logistic regression identified age ≥ 65 (OR: 8.66; 95% CI: 1.86, 40.34; P = 0.006), length of hospital stays (OR: 1.23; 95% CI: 1.03, 1.47; P = 0.022), and baseline consolidation volume as a percentage of the whole lung (OR: 56.95; 95% CI: 1.198, 2706.782; P = 0.04) as independent risk factors for persistent CT lung abnormalities at 1 year. After 1 year, 34.38% (22/64) of patients still had abnormal lung function, and 9.38% (6/64) had pulmonary fibrosis and restrictive ventilatory dysfunction. The relationship between lung function and CT findings is weak correlation. The mixed model analysis revealed significant differences between groups, particularly between the moderate and severe groups, and significant changes in CT values over time. One year after infection, more than one third of even moderate patients with mild symptoms had persistent pulmonary abnormalities. In our study, fibrotic changes were seen in severe and critically ill patients and remained stable 6 months after discharge from hospital. Imaging parameters can predict the prognosis. The larger the extent of baseline consolidation, the worse the prognosis of elderly patients.

Effect of POD24 on the prognosis of follicular and other indolent B-cell non-hodgkin lymphomas.

Indolent B-cell non-Hodgkin lymphomas(B-NHL) encompass a heterogeneous category of lymphomas characterized by a wide range of pathological subtypes. With the application of chemoimmunotherapy with rituximab (R-chemo), the prognosis of patients has improved considerably, with a 10-year survival rate of 60-80%. Despite these advancements, a significant number of patients still experience disease progression during or shortly after initial treatment. Those who progress within the first 24 months (POD24) continue to face a notably worse prognosis. This study aims to explore the significance of POD24 in predicting the prognosis of different subtypes of indolent B-cell NHL through a comprehensive literature review. The investigation extends to examining the existing prognostic assessment tools and evaluating the interrelationship between POD24 and these tools. By synthesizing relevant research findings, this study seeks to contribute to the current understanding of the role POD24 plays in prognostic evaluation and its potential implications in guiding clinical decision-making for patients with indolent B-cell NHL.

Deciphering the SOX4/MAPK1 regulatory axis: a phosphoproteomic insight into IQGAP1 phosphorylation and pancreatic Cancer progression

ObjectiveThis study aims to elucidate the functional role of IQGAP1 phosphorylation modification mediated by the SOX4/MAPK1 regulatory axis in developing pancreatic cancer through phosphoproteomics analysis.MethodsProteomics and phosphoproteomics data of pancreatic cancer were obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Differential analysis, kinase-substrate enrichment analysis (KSEA), and independent prognosis analysis were performed on these datasets. Subtype analysis of pancreatic cancer patients was conducted based on the expression of prognostic-related proteins, and the prognosis of different subtypes was evaluated through prognosis analysis. Differential analysis of proteins in different subtypes was performed to identify differential proteins in the high-risk subtype. Clinical correlation analysis was conducted based on the expression of prognostic-related proteins, pancreatic cancer typing results, and clinical characteristics in the pancreatic cancer proteomics dataset. Functional pathway enrichment analysis was performed using GSEA/GO/KEGG, and most module proteins correlated with pancreatic cancer were selected using WGCNA analysis. In cell experiments, pancreatic cancer cells were grouped, and the expression levels of SOX4, MAPK1, and the phosphorylation level of IQGAP1 were detected by RT-qPCR and Western blot experiments. The effect of SOX4 on MAPK1 promoter transcriptional activity was assessed using a dual-luciferase assay, and the enrichment of SOX4 on the MAPK1 promoter was examined using a ChIP assay. The proliferation, migration, and invasion functions of grouped pancreatic cancer cells were assessed using CCK-8, colony formation, and Transwell assays. In animal experiments, the impact of SOX4 on tumor growth and metastasis through the regulation of MAPK1-IQGAP1 phosphorylation modification was studied by constructing subcutaneous and orthotopic pancreatic cancer xenograft models, as well as a liver metastasis model in nude mice.ResultsPhosphoproteomics and proteomics data analysis revealed that the kinase MAPK1 may play an important role in pancreatic cancer progression by promoting IQGAP1 phosphorylation modification. Proteomics analysis classified pancreatic cancer patients into two subtypes, C1 and C2, where the high-risk C2 subtype was associated with poor prognosis, malignant tumor typing, and enriched tumor-related pathways. SOX4 may promote the occurrence of the high-risk C2 subtype of pancreatic cancer by regulating MAPK1-IQGAP1 phosphorylation modification. In vitro cell experiments confirmed that SOX4 promoted IQGAP1 phosphorylation modification by activating MAPK1 transcription while silencing SOX4 inhibited the proliferation, migration, and invasion of pancreatic cancer cells by reducing the phosphorylation level of MAPK1-IQGAP1. In vivo, animal experiments further confirmed that silencing SOX4 suppressed the growth and metastasis of pancreatic cancer by reducing the phosphorylation level of MAPK1-IQGAP1.ConclusionThe findings of this study suggest that SOX4 promotes the phosphorylation modification of IQGAP1 by activating MAPK1 transcription, thereby facilitating the growth and metastasis of pancreatic cancer.

Identification of subgroups and development of prognostic risk models along the glycolysis–cholesterol synthesis axis in lung adenocarcinoma

Lung cancer is one of the most dangerous malignant tumors affecting human health. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Both glycolytic and cholesterogenic pathways play critical roles in metabolic adaptation to cancer. A dataset of 585 LUAD samples was downloaded from The Cancer Genome Atlas database. We obtained co-expressed glycolysis and cholesterogenesis genes by selecting and clustering genes from Molecular Signatures Database v7.5. We compared the prognosis of different subtypes and identified differentially expressed genes between subtypes. Predictive outcome events were modeled using machine learning, and the top 9 most important prognostic genes were selected by Shapley additive explanation analysis. A risk score model was built based on multivariate Cox analysis. LUAD patients were categorized into four metabolic subgroups: cholesterogenic, glycolytic, quiescent, and mixed. The worst prognosis was the mixed subtype. The prognostic model had great predictive performance in the test set. Patients with LUAD were effectively typed by glycolytic and cholesterogenic genes and were identified as having the worst prognosis in the glycolytic and cholesterogenic enriched gene groups. The prognostic model can provide an essential basis for clinicians to predict clinical outcomes for patients. The model was robust on the training and test datasets and had a great predictive performance.

Long-term outcomes among ischemic stroke TOAST subtypes: A 12-year Cohort study in China

BackgroundDisparities in short-term ischemic stroke (IS) prognosis among Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes were observed. Notably, little is known about the long-term prognosis of different subtypes in China. We aim to investigate the long-term outcome in IS patients and try to explore the potential interactive effects between IS subtypes and antithrombotic therapy. MethodsThis is a prospective cohort of stroke survivors. Patients diagnosed with first-ever IS at the Department of Neurology, West China Hospital, Sichuan University from January 2010 to December 2019 were recruited. They were followed until September 2022 to assess recurrence, mortality, and functional recovery. The multivariate Fine-Gray model assessed stroke recurrence, while Cox regression estimated hazard ratios. Modified Rankin Scale scores(mRS) were analyzed using the generalized linear mixed effects model. ResultsAt baseline, 589 of 950 participants (62.00 %) were male. The longest follow-up was 150 months, the shortest was 1.5 months, and the median follow-up was 81.0 months. Cardio-embolism (CE) bore the highest mortality risk compared to large artery atherosclerosis (LAA) (HR=4.43,95 %CI 1.61-12.23). Among survivors on anticoagulant therapy, CE exhibited a reduced risk of mortality (HR = 0.18, 95 % CI 0.04-0.80). In function recovery, small artery occlusion (SAO) demonstrated more favorable prognostic outcomes (β=-2.08, P<0.01, OR=0.13,95 %CI 0.03-0.47). Among survivors taking antiplatelet drugs, SAO demonstrated a slower pace of functional recovery compared to LAA (β=1.39, P=0.05, OR=3.99,95 %CI 1.01-15.74). ConclusionsLong-term outcomes post-first IS vary among TOAST subtypes. Anticoagulant therapy offers long-term benefits among patients of the CE. However, prolonged administration of antiplatelet drugs among SAO patients may be limited in improving function recovery. Physicians should carefully consider treatment options for different IS subtypes to optimize patient outcomes and stroke care effectiveness.

Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: ① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ (P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

Abstract PO2-08-02: Evaluation of predictive and prognostic value of androgen receptorexpression in breast cancer subtypes treated with neoadjuvantchemotherapy

Abstract Background Neoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored. Methods We retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed. Results The positive rates of AR expression in HR +/HER2-, HR +/HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR +/HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR +/HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer. Conclusions AR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR +/HER2- subtype and in HR +/HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P= 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P &amp;lt; 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR +/HER2- and HR +/HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis Citation Format: Jin Zhang. Evaluation of predictive and prognostic value of androgen receptorexpression in breast cancer subtypes treated with neoadjuvantchemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-02.

Analysis and insights of cardiac amyloidosis: novel perception of rare diseases in cardiology.

Amyloidosis is a rare systemic disease, while cardiac amyloidosis (CA) is nothing more than a chronic disease that causes fatal damage to the structure and function of the heart. The pathogenesis of CA is elusive, the clinical manifestations are diverse and lack of specificity, and the treatment and prognosis of different subtypes vary widely. It is of great practical significance to deepen the understanding of CA. The clinical data of 39 patients with CA admitted to the First Affiliated Hospital of Gannan Medical University and Fujian Medical University Union Hospital from January 1, 2018 to March 1, 2024 were collected and retrospectively studied, and the clinical features, diagnosis, differentiation, treatment effects and prognosis of CA patients were analyzed. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of CA. This paper is expected to provide novel and valuable references for the clinical and basic research of CA. A total of 39 patients with CA were included in this study, including 23 males (58.97%) and 16 females (41.03%). The average age at diagnosis was 60.51±10.28 years old. In this study, 24 patients (61.54%) had anemia of different degrees, 19 patients (48.72%) were accompanied by abnormal elevation of cardiac troponin T (cTnT), and all patients (100%) had abnormal elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP), and 28 patients (71.79%) had renal impairment. Typical electrocardiogram (ECG) findings in CA patients in this study show low voltage in limb leads, various types of atrioventricular block, various types of tachycardia, atrial fibrillation and poor R-wave progression. The representative results of ultrasonic cardiogram (UCG) showed: 1. Atrium were enlarged, and ventricular wall motion was weakened. 2. Septum and posterior walls of the ventricle were symmetrically thickened, and the myocardium showed speckled strong echo. 3. Mitral regurgitation (moderate to severe) and tricuspid regurgitation. 4. Widening of the pulmonary artery and pulmonary hypertension. Typical results of cardiac magnetic resonance imaging (MRI) of CA patients in this study showed that delayed gadolinium enhancement of the ventricular wall, with ventricular wall thickening to varying degrees and ventricle or atrium enlargement. The pathological manifestations of CA patients in this study were mostly Congo red staining (+) and deposition of eosinophilic amyloid in the affected organs or tissues. All CA patients included in this study received standardized treatment, the median follow-up time was 29.5 (range, 6.5-71) months, and at the latest follow-up, only 12 cases of 39 patients with CA were still alive, and 27 patients died in our study, all of which were due to uncontrollable progression of the disease and failed treatment. Our study showed that there is no statistical significance in the different age groups of the CA patients (P>0.05), while it was surprising that male CA patients had significantly worse overall survival (OS) than female patients. Correspondingly, patients who received chemotherapy and were accompanied with renal impairment had a worse prognosis than those who did not receive chemotherapy and had normal renal function (all P<0.05). CA is a rare disease caused by systemic amyloidosis, the pivotal points of CA diagnosis and treatment as well as the premise for improving the long-term prognosis of CA patients are clear diagnosis and accurate typing. The treatment of CA also requires targeted individual treatment according to the subtype and etiology of CA patients, so as to maximize the prognosis of CA patients.

Long-Term Prognosis of Different Subtypes of Left Ventricular Noncompaction Cardiomyopathy Patients: A Retrospective Study in China.

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National Cancer Database-Breast Cancer Registry.

Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC. We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups. For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases. Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC.

Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy

BackgroundNeoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored.MethodsWe retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed.ResultsThe positive rates of AR expression in HR + /HER2-, HR + /HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR + /HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR + /HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer.ConclusionsAR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR + /HER2- subtype and in HR + /HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P = 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P < 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR + /HER2- and HR + /HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis.

Prognostic disparities in young patients based on breast cancer subtype: A population-based study from the SEER database.

Triple-negative breast cancer (TNBC) is associated with younger age and worse long-term survival. However, the characteristics and prognosis of different subtypes of breast cancer (BC) in young (<40 years) patients have not yet been elucidated. The present population-based study explored the clinical and pathological characteristics of young TNBC patients and investigated their long-term survival. We enrolled patients from the Surveillance, Epidemiology, and End Results database younger than 40 years of age with primary BC. Cases were defined as patients with TNBC (hormone receptor [HR]-/human epidermal growth factor receptor 2 [HER2]-), and controls were patients with other subtypes of BC (HR-/HER2+, HR+/HER2-, and HR+/HER2+). Demographic, pathological, and radiotherapy, chemotherapy, and surgery data were extracted and the overall survival was the primary endpoint. We enrolled 14,234 young patients with BC in the present study, of whom 2798 (19.7%) had TNBC and 11,436 (80.3%) had another BC subtype. A higher proportion of TNBC patients than non-TNBC patients had a more advanced tumor-node-metastasis stage (II-IV 80.5% vs 73.1%, P < .001), and smaller proportions underwent radiotherapy (50.0% vs 53.3%, P = .002) and surgery (91.8% vs 92.9%, P < .001). TNBC was associated with significantly lower 5-year survival rates than other subtypes among patients with regional node positivity (0, 1-3, 4-9, ≥10: 54.2% vs 57.7%, 44.2% vs 55.9%, 31.0% vs 52.0%, and 27.7% vs 38.8%, P < .001) and those with different lymph node ratios (low, intermediate, high: 50.9% vs 56.0%, 34.6% vs 53.6%, and 24.8% vs 44.8%, P < .001). Our research is the first to investigate the relevant characteristics of young TNBC patients in comparison with those of young non-TNBC patients based on the surveillance, epidemiology, and end results database. We found that young TNBC patients have a higher pathological stage and worse long-term survival than young patients with other BC subtypes. These findings have implications in identifying young patients with TNBC for aggressive therapy and further investigations should be performed to explore new multimodal treatments for such patients.

Abstract P4-02-25: Analysis of prognosis in different subtypes of invasive lobular carcinoma using a National Cancer Database Breast Cancer Registry of Japan

Abstract [Introduction] Invasive lobular carcinoma (ILC) has different pathological and clinical features from invasive ductal carcinoma (IDC). ILC has more likely to be hormone receptor (HR) positive, and several studies reported that the prognosis of ILC was better than IDC. However, ILC also has different prognosis according to the subtypes as IDC does, and better prognosis of ILC might depend on their high HR positivity. Additionally, there are many reports that chemotherapy (CT) does not improve the prognosis of ILC due to the high positivity of HR. Therefore, we compared the prognosis of ILC and IDC in the same subtypes and considered necessity of CT for luminal ILC. ILC usually constitutes small population of invasive breast cancer. Thus, we have planed the analysis by using the Breast Cancer Registry (BCR) run on the National Cancer Database (NCD) in Japan. [Methods] 318,338 breast cancer patients were registered in BCR between 2004 and 2012. We selected 250,736 patients who were diagnosed as ILC or IDC. Patients with distant metastasis, those who did not receive surgery, and those who received preoperative therapy, and those who had bilateral breast cancer were excluded, and it resulted in 207,428 patients. Of these cases, the cases with 10-year follow-up data were 136,654, and we examined 5,705 ILC and 130,949, IDC. Because it was presumed that there are differences in pathological and clinical characteristics between ILC and IDC, we have planned to make the matched cohorts by using exact matching for comparing their prognosis. To evaluate the prognosis of each subtype, we compared DFS and OS for IDC and ILC in each subtype. To evaluate the effect of CT in luminal ILC, we corrected the data of luminal ILC with pT2N0M0 or pT1-2N1M0 patients and compared DFS and OS between endocrine therapy (ET) only group and ET+CT group. DFS was defined as the time from surgery to local or distant recurrence or death from any cause. OS was defined as the time between the surgery and the death from any cause. Peason’s Chi squared test was used to identify the characteristics. Survival curves were constructed by Kaplan-Meier method and were compared by log-rank test. [Results] We made the matched cohort by using exact matching and we identified 5,633 ILC and 5,633 IDC for prognosis analysis. In overall subtypes, the 10-year DFS of ILC was poor than those of IDC (76.56% vs 79.14%, p=0.04). In the analysis by each subtype, there was no statistical difference in DFS for luminal HER2, HER2, and TN cohorts, however luminal ILC had statistically significant poor DFS than luminal IDC (78.04% vs 81.17%, p&amp;lt; 0.01). The analysis of 10-year OS showed similar results, and there were no differences in the OS of luminal HER2, HER2 and TN cohorts between ILC and IDC. However, ILC had worse OS than IDC in luminal cohort (85.95% vs 89.13%, p&amp;lt; 0.01). To evaluate the effect of CT in luminal ILC, we made the matched cohort and we identified 95 luminal IDC and 95 luminal ILC in pT2N0 cohort, and 83 luminal IDC and 83 luminal ILC in pT1-2N1 cohort for the analysis. In pT2N0 cohort, the 10-year DFS was 82.12% in ET+CT group and 87.35% in ET only group (p=0.99). The OS of the ET+CT and the ET only group was 93.48% and 94.04% (p=0.88). In pT1-2N1 cohort, the ET only group had 54.17% and the ET+CT group had 77.03% of DFS (p=0.34). The OS in the ET only group and the ET+CT group was 61.96% and 94.81% (p=0.01). [Discussion] Although luminal HER2, HER2 and TN cohorts had no differences in prognosis between ILC and IDC, luminal ILC had a poor prognosis than luminal IDC. Therefore, luminal ILC needs stronger approach to improve their prognosis. And it was suggested that chemotherapy is effective for recurrent high-risk luminal ILC such as those with positive lymph node metastasis. [Conclusion] ILC had worse prognosis than IDC in luminal cohort, however it was comparable in luminal HER2, HER2, TN cohorts. A new strategy of treatments for luminal ILC might be needed to improve their prognosis. Citation Format: Yayoi Adachi, Sota Asaga, Hiraku Kumamaru, Yutaka Yamamoto, Shigeru Imoto, Hiromitsu Jinno. Analysis of prognosis in different subtypes of invasive lobular carcinoma using a National Cancer Database Breast Cancer Registry of Japan [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-25.

Clinicopathological characteristics of mixed neuroendocrine-non-neuroendocrine neoplasms in gastrointestinal tract.

In 2019, the World Health Organization (WHO) classification system updated the definition of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), previously known as mixed adenoneuroendocrine carcinomas (MANECs). The clinicopathological characteristics of this new definition remains to be clarified. We analyzed the clinical data of 43 patients diagnosed with MiNENs in Wuhan Union Hospital from 2011 to 2020 according to the definition of MiNENs proposed in 2019. Among the 43 patients with MiNENs, the top two most common sites were stomach and colon, and 69.8% were males. Nearly half (21/43) of the patients were diagnosed at TNM stage III, and about 53.5% (23/43) of patients were the neuroendocrine neoplasm dominant type. Among the non-neuroendocrine tumor components of 43 MiNENs patients, adenocarcinoma accounted for 95.3% (41/43) and squamous cell carcinoma accounted for 4.7% (2/43)；95.3% (41/43) of the neuroendocrine neoplasm components were neuroendocrine carcinoma (NEC) and 4.7% (2/43) were neuroendocrine tumor (NET). Approximately 60.5% (26/43) neuroendocrine components had a Ki-67 index ≥55%. In addition, we further compared the prognosis of different subtypes of the MiNENs based on the neuroendocrine neoplasm component and non-neuroendocrine neoplasm component, and the results showed that there was no significant difference in survival between different subtypes of MiNENs (P>0.05). MiNENs can exhibit diverse clinicopathological characteristics, and there is no significant difference in prognosis among MiNENs subtypes, indicating that the definition of MiNENs can well summarize the prognosis of this type of tumor.

Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis

ObjectiveThe aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA.MethodsWe reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA.ResultsA total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405–20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011–0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060–0.696 p = 0.011) were related to improved survival.ConclusionThe clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.

The expression of HOXC10 is correlated with tumor-infiltrating immune cells in basal-like breast cancer and serves as a prognostic biomarker.

BackgroundHomeobox gene C10 (HOXC10) plays a vital role in the occurrence and development of several cancers, but its effects and underlying mechanism in the prognosis of different subtypes of breast cancer remain unclear.MethodsFirst, we evaluated and compared the expression levels of HOXC10 cancer to normal tissues in the Oncomine and Tumor Immune Estimation Resource (TIMER) databases. Second, the correlation between HOXC10 and the survival of patients with different types of cancer, including breast cancer, was analyzed in the PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter databases. Finally, the relationship between HOXC10 and immune-infiltration levels or gene marker sets of immune cells in basal-like breast cancer (BLBC) was investigated in the TIMER and GEPIA databases.ResultsThe expression of HOXC10 was elevated in breast cancer tissues. High HOXC10 expression indicated a poor prognosis for breast cancer patients, and expression affected the survival time of lymph-node positive or grade III breast cancer patients. In BLBC, the median overall survival (OS) of patients with high HOXC10 expression was significantly shorter than that of patients with low HOXC10 expression. HOXC10 was positively correlated with the immune infiltration of macrophages in BLBC. Breast cancer patients with low HOXC10 expression in different enriched immune-cell subgroups had a favorable prognosis.ConclusionsThe level of HOXC10 expression increased significantly in breast cancer, and elevated HOXC10 was positively correlated with immune-cell infiltration and poor prognosis in BLBC. These findings shed light on the important role of HOXC10 in breast cancer. HOXC10 should be recognized as a prognostic biomarker for determining prognosis and immune infiltration in BLBC patients.

High FAS expression correlates with a better prognosis and efficacy of taxanes and target regents in breast cancer.

FAS can serve as both an oncogene and a suppresser in different malignancies, and the prognostic value of FAS remains controversial. The Oncomine database, KM-Plotter and bc-GenExMiner platform were adopted to analyze the prognostic value of FAS in breast cancer. Breast cancer tissue microarrays were further used to verify these data. The Cell Miner Tool was used to predict the value of FAS mRNA expression in predicting the efficacies of clinical drugs. We found that both FAS mRNA and protein expression level significantly reduced in breast carcinoma. In addition, high FAS expression indicates a better metastatic relapse-free survival. Interestingly, FAS was associated with a better prognosis in different subtypes of breast cancer patients, namely, only in grade II and III, lymph nodal positive or p53 wild-type patients. The data from the Cell Miner Tool revealed that FAS mRNA expression was correlated with the efficacy of the first-line chemotherapeutic taxane agents and target drugs including olaparib and everolimus. FAS expression correlates with a better prognosis in breast cancer and may provide an effective clinical strategy to predict the sensitivity of taxanes and targeted drugs.

Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment.

Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC.Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163. Correlations between LATS1/2 expression and immune-related markers were investigated and the prognoses of patients with different GC subtypes were analyzed.Results: CD8 and CD163 appeared to be favorable and adverse prognostic factors, respectively. LATS1/2 and FOXP3 did not predict patients' overall survival. However, in microsatellite-stable GC patients, high LATS1/2 and FOXP3 expression and low CD8 expression predicted poor prognoses. Furthermore, high LATS1/2 expression was significantly correlated with decreased CD8 and increased FOXP3. Combined analysis of LATS1/2, CD8, and FOXP3 had better prognostic accuracy than did each marker individually.Conclusions: Different biological molecules can predict the prognoses of different types of GC patients. LATS1/2, core kinases in the Hippo pathway, are closely related to CD8 and FOXP3. Further understanding the mechanisms of LATS1/2 in CD8+ T cells and FOXP3+ Treg cells provides further theoretical basis and potential targets for GC immunotherapy.

Predicting the invasiveness of lung adenocarcinomas appearing as ground-glass nodule on CT scan using multi-task learning and deep radiomics.

BackgroundDue to different treatment method and prognosis of different subtypes of lung adenocarcinomas appearing as ground-glass nodules (GGNs) on computed tomography (CT) scan, it is important to classify invasive adenocarcinomas from non-invasive adenocarcinomas. The purpose of this paper is to build and evaluate the performance of deep learning networks on the differentiation the invasiveness of lung adenocarcinoma appearing as GGNs.MethodsThis retrospective study included 886 GGNs from 794 pathological confirmed patients with lung adenocarcinoma for training and testing the proposed networks. Three deep learning networks, namely XimaNet (deep learning-based classification model), XimaSharp (classification and nodule segmentation model), and Deep-RadNet (deep learning and radiomics combined classification model, i.e., deep radiomics) were built. Three classification tasks, namely task 1: classification of AAH/AIS and MIA, task 2: classification of MIA and IAC, and task 3: classification of non-invasive adenocarcinomas and invasive adenocarcinomas (AAH/AIS&MIA and IAC) were conducted to evaluate the model performance. The Z-test was used to compare the model performance.ResultsThe AUC for classification of AAH/AIS with MIA were 0.891, 0.841 and 0.779 for Deep-RadNet, XimaNet and XimaSharp respectively. The AUC for classification of MIA with IAC were 0.889, 0.785 and 0.778 for three networks and AUC for classification of AAH/AIS&MIA with IAC were 0.941, 0.892 and 0.827 respectively. The performance of deep_RadNet was better than the other two models with the Z-test (P<0.05).ConclusionsDeep-RadNet with the visual heat map could evaluate the invasiveness of GGNs accurately and intuitively, providing a theoretical basis for individualized and accurate medical treatment of patients with GGNs.

Identification of tumor microenvironment-related genes in lower-grade gliomas by mining TCGA database.

BackgroundLower-grade gliomas (LGGs) are ubiquitous and fatal branches of brain neoplasm. Finding biomarkers related to diagnosis and treatment is essential for the treatment of LGG. It is possible to reveal the potential links between tumor microenvironment and overall survival (OS) in LGG by mining the mRNA expression profile from the TCGA database. Our primary purpose was to explore key genes that can be applied for diagnosis or treatment in LGG microenvironment.MethodsBased on the ESTIMATE algorithm, the immune and stromal scores were calculated to measure the extent of infiltration of immune cells and stromal cells, respectively. The LGG samples from TCGA database were assigned into high- or low-score groups per the immune and stromal scores and differentially expressed genes (DEGs) were selected by comparing gene expression levels in the two groups. Functional enrichment analysis and protein-protein interaction (PPI) networks were performed to analyze DEGs. Finally, selected DEGs were validated using another independent LGG cohort from CGGA dataset.ResultsThe results indicated that immune/stromal scores correlated with LGG prognosis. Furtherly, survival analysis conducted for each subtype shown that immune/stromal scores were only significantly associated with the prognosis of astrocytoma, IDH-wildtype, and there was no significant statistical difference in the other subtypes. Functional enrichment analysis and protein-protein interaction (PPI) networks further showed that the upregulated DEGs were primarily involved in immune response, plasma membrane, and cytokine binding. Accordingly, a series of genes that have significant impacts on prognosis and are significantly associated with the tumor microenvironment were obtained.ConclusionsBased on the ESTIMATE algorithm, we first explored the relationship between immune/stromal scores and prognosis in different subtypes of LGG and the result shown that the scores were only strongly associated with the prognosis of astrocytoma, IDH-wildtype. Furtherly, a comprehensive bioinformatics analysis of the gene expression profiles of astrocytoma, IDH-wildtype patients was conducted, CASP8, TRIM6, TRIM38, PARP9, NMI, EPSTI1, DTX3L and AGBL2 were identified as tumor microenvironment-related genes, may be involved in the occurrence, development, and invasion of LGG.