Independent Predictor Of Poor Prognosis Research Articles

Deep learning prediction of survival in patients with heart failure using chest radiographs.

Heart failure (HF) is associated with high rates of morbidity and mortality. The value of deep learning survival prediction models using chest radiographs in patients with heart failure is currently unclear. The aim of our studyisto develop and validate a deep learning survival prediction model using chest X-ray (DLSPCXR) in patients with HF. The study retrospectively enrolled a cohort of 353 patients with HF who underwent chest X-ray (CXR) at our institution between March 2012 and March 2017. The dataset was randomly divided into training (n = 247) and validation (n = 106) datasets. Univariate and multivariate Cox analysis were conducted on the training dataset to develop clinical and imaging survival prediction models. The DLSPCXR was trained and the selected clinical parameters were incorporated into DLSPCXR to establish a new model called DLSPinteg. Discrimination performance was evaluated using the time-dependent area under the receiver operating characteristic curves (TD AUC) at 1, 3, and 5-years survival. Delong's test was employed for the comparison of differences between two AUCs of different models. The risk-discrimination capability of the optimal model was evaluated by the Kaplan-Meier curve. In multivariable Cox analysis, older age, higher N-terminal pro-B-type natriuretic peptide (NT-ProBNP), systolic pulmonary artery pressure (sPAP) > 50mmHg, New York Heart Association (NYHA) functional class III-IV and cardiothoracic ratio (CTR) ≥ 0.62 in CXR were independent predictors of poor prognosis in patients with HF. Based on the receiver operating characteristic (ROC) curve analysis, DLSPCXR had better performance at predicting 5-year survival than the imaging Cox model in the validation cohort (AUC: 0.757 vs. 0.561, P = 0.01). DLSPinteg as the optimal model outperforms the clinical Cox model (AUC: 0.826 vs. 0.633, P = 0.03), imaging Cox model (AUC: 0.826 vs. 0.555, P < 0.001), and DLSPCXR (AUC: 0.826 vs. 0.767, P = 0.06). Deep learning models using chest radiographs can predict survival in patients with heart failure with acceptable accuracy.

Влияние поражения сердца на прогноз у пациентов с системным AL-амилоидозом

AIM. To assess the clinical features as well as the factors affecting prognosis and long-term treatment outcomes in systemic AL amyloidosis patients with cardiac involvement. MATERIALS &amp; METHODS. The trial enrolled 123 systemic AL amyloidosis patients with cardiac involvement who were treated at the RM Gorbacheva Scientific Research Institute in 2004–2023. The patients were 34–85 years of age (median 61 years); there were 61 women (49.6 %) and 62 men (50.4 %). RESULTS. Cardiac disease grades 1, 2, 3a, and 3b were identified in 13.8 %, 50.4 %, 17.9 %, and 17.9 % of AL amyloidosis patients, respectively. Chronic cardiac failure (CCF) developed in 65.9 % (n = 81), and severe cardiac failure was detected in 25.4 % (n = 31) of patients. Most of them (90,2 %), despite CCF, preserved left ventricular ejection fraction (&gt; 40 %) with the mean value of 59.6 % (range 33–78 %). The left ventricular stroke volume index (SVI) was below the normal values (&lt; 41 mL/m2) in 92.7 % of patients. The mean SVI value was 26.1 mL/m2 (range 8.3–49.5 mL/m2). The lower SVI was associated with cardiac disease grades. This parameter appeared to be 30.9 mL/m2, 26.8 mL/m2, 24.8 mL/m2, and 21.4 mL/m2 in grades 1, 2, 3a, and 3b (p = 0.006), respectively. Total global strain (TGS) in the left ventricle myocardium was decreased (&lt; 20 %) in 94.6 % of patients. The mean TGS value was 13.8 % (range 4.4–34.8 %). TGS was diminishing with increasing cardiac disease grade (grade 1 with 17.8 %, grade 2 with 14.6 %, grade 3a with 13.1 %, and grade 3b with 9.6 %) (p = 0.007). Atrial fibrillation was reported in 23 % of patients, supraventricular tachycardia was observed in 31.9 %, and supraventricular extrasystoles were registered in 39.7 %. Ventricular extrasystoles were found in 73.7 % of patients, and ventricular tachycardia was seen in 13.2 %. Sinoatrial block was reported in 6.6 % of patients, and atrioventricular block was identified in 19.8 %. Syncope occurred in 12.3 % of patients. An artificial cardiac pacemaker was implanted in 8 patients. The thromboembolism rate was 13 %: the myocardial infarction rate was 11.4 %, and the rate of acute cerebrovascular accidents was 5.7 %. Atrial clots were detected in 2 (1.6 %) patients. The cumulative incidence of hematologic response for 2 years was 57 % and did not depend on cardiac disease grade, the 2-year rate of cardiac response was 39.1 %. Before achieving hematologic and cardiac responses, mortality was 26.5 % and 29.9 %, respectively. The overall 5-year survival was 62.6 %, and the 5-year hematologic progression-free and major organ impairment-free survival was 39.3 %. Cox regression model confirmed 3 independent predictors of poor prognosis: the level of NT-proBNP ≥ 2500 pg/mL (p = 0.004), SVI &lt; 25 mL/m2 (p = 0.0174), and prior syncope (p = 0.0191). The achievement of hematologic response had a positive effect on survival rates (p &lt; 0.0001). CONCLUSION. A comprehensive assessment of cardiac damage by the time of primary AL amyloidosis diagnosis as well as appropriate treatment of this disease can reduce the risk of early cardiac mortality and enhance chances of not only achieving hematologic response but also improving survival rates.

Prognostic impact of FAN score in patients receiving nivolumab plus ipilimumab for metastatic renal cell carcinoma

FAN score is reportedly associated with prognostic outcomes in patients with urothelial carcinoma being treated with immune check point inhibitors. However, the prognostic impact of pre-treatment FAN score in patients with metastatic renal cell carcinoma (RCC) treated with nivolumab plus ipilimumab remains unclear. We retrospectively evaluated the association between pre-treatment FAN score and prognostic outcomes in 154 patients with metastatic RCC treated with nivolumab plus ipilimumab. The pre-treatment FAN score was ‘0’ in 56 patients (36%), ‘1’ in 60 patients (40%), ‘2’ in 37 patients (24%) and ‘3’ in one patient (1%). Progression-free survival was not significantly different between patients with different FAN scores, but second progression-free survival (PFS2), cancer-specific survival (CSS) and overall survival (OS) were significantly different. In multivariable Cox proportional hazard analyses, FAN score ≥ 2 was a significant predictor of poor PFS2 (vs. FAN score 0, HR: 2.43, 95% CI 1.21–4.87, P = 0.01), poor CSS (vs. FAN score 0, HR: 2.71, 95% CI 1.13–6.47, P = 0.02) and poor OS (vs. FAN score 0, HR: 2.42, 95% CI 1.11–5.25, P = 0.02). High pre-treatment FAN score could be a significant independent predictor of poor prognosis in patients receiving nivolumab plus ipilimumab for metastatic RCC.

Analysis of clinical features and prognostic factors in Takayasu arteritis involving pulmonary hypertension: A retrospective study.

Multiple takayasu arteritis (TA) is a chronic nonspecific large to medium vasculitis disease that mainly accumulates the aorta and its branches. Pulmonary vascular disease is often seen as stenosis and occlusion, and patients may show no moderate to severe pulmonary hypertension (PH). This study aims to summarize the clinical characteristics and analysis of prognostic factors in patients with PH caused by TA. Patients diagnosed with aortitis involving the pulmonary artery by pulmonary arteriography or pulmonary artery and total aortic computed tomography arteriography (CTA). All patients underwent detailed clinical assessment, laboratory data collection, and analysis of imaging data. Patients were followed up and factors affecting the prognosis of the pulmonary arteries were analyzed. Most of the patients' complaints were chest tightness, shortness of breath, decreased activity tolerance, hemoptysis and chest pain. 56.90% of the patients were in at the time of admission. Echocardiographic estimation of pulmonary artery systolic pressure was 90.39 ± 22.87 mm Hg. In terms of laboratory tests, 39.66%% of the patients had elevated C-reactive protein and erythrocyte sedimentation rate, and amino-terminal natriuretic peptide precursor on admission. In terms of imaging, all patients had pulmonary artery involvement, which was combined with aortic involvement in 31.03%. Nuclide lung perfusion/ventilation imaging of the patients revealed multiple perfusion defects/absences in the segmental and subsegmental distribution of the lungs. Univariate Cox regression model analysis suggested that patients' WHO functional class at admission, age ≧ 51 years at the time of consultation, and amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL were factors affecting the prognosis. Further multifactorial Cox regression model analysis suggested amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL was an independent predictor of poor prognosis with a hazard ratio (HR) value of 5.248. Electrocardiogram and echocardiogram may suggest an increased right heart load; some patients have elevated serum inflammatory indexes. Characteristic imaging manifestations include widening of the main pulmonary artery, multiple pulmonary segmental and subsegmental stenoses.

Abstract PO1-07-11: Radiogenomic-based imaging intratumor heterogeneity model predicts breast cancer prognosis and unveils therapeutic targets

Abstract Background: Intratumor heterogeneity (ITH) refers to variations observed among cancer cells within a single tumor, posing significant challenges in clinical practice due to its contribution to treatment resistance and unfavorable outcome. However, the inconvenience of multi-region biopsy and limitations of genomic sequencing based on limited tissue impede the practical detection of ITH. Consequently, there is an urgent need for a non-invasive method that comprehensively captures ITH from a holistic perspective of the entire tumor. Methods: We utilized a large multicenter dataset comprising dynamic contrast-enhanced magnetic resonance images from breast cancer patients (n = 1423) along with matched multiomics data (n = 468) to develop a non-invasive machine learning approach for measuring ITH. We extracted quantitative radiomic features from both the entire tumor and peritumor regions, with a specific focus on features associated with imaging heterogeneity. Using these radiomic features, we established an imaging ITH (IITH) model. The robustness of IITH evaluation was determined by assessing its correlation with genomic ITH (employing the mutant-allele tumor heterogeneity [MATH] algorithm) and pathological cellular ITH (analyzing variation in quantitative nuclear features extracted through digital pathology). Prognostic power was evaluated using Kaplan-Meier and multivariate Cox proportional hazards analyses. Integrated multiomics analyses were performed to investigate the molecular basis of different IITH subgroups. Results: We developed a non-invasive radiomic signature to quantify imaging ITH (IITH) in the FUSCC cohort. Breast cancer patients were retrospectively categorized into high and low IITH groups. Multivariate Cox analysis identified high IITH as an independent predictor of poor prognosis in breast cancer patients, even after adjusting for clinical risk factors such as tumor size, positive lymph nodes, clinical subtype and lymphovascular invasion status. These findings were further validated in the DUKE cohort, confirming the prognostic value of IITH. Moreover, we substantiated the robustness of IITH by demonstrating its association with genomic and pathological ITH. Multiomics analysis revealed the activation of oncogenic pathways and metabolic dysregulation in high-IITH tumors. Intriguingly, our investigation also highlighted ferroptosis as a vulnerability and potential therapeutic target in high-IITH tumors, which was further supported by evidence from the TCGA cohort. Conclusion: Radiomic-based assessment of ITH provides a non-invasive approach to comprehensively capture ITH and predict the prognosis of breast cancer patients. Targeting ferroptosis may hold promise as a treatment strategy for patients with high IITH. Citation Format: Guan-Hua Su, Yi Xiao, Chao You, Ren-Cheng Zheng, Shen Zhao, He Wang, Yi-Zhou Jiang, Ya-Jia Gu, Zhi-Ming Shao. Radiogenomic-based imaging intratumor heterogeneity model predicts breast cancer prognosis and unveils therapeutic targets [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 PO1-07-11.

Effect of mean platelet volume and platelet count on the prognosis of branch atheromatous disease.

The purpose of this study was to investigate the predictive value of mean platelet volume (MPV) and platelet count (PC) in branch atheromatous disease (BAD). This retrospective study included 216 patients with BAD-stroke within 48h of symptom onset. These patients were divided into good and poor prognosis groups according to their 3-month modified Rankin scale scores after discharge. Multiple logistic regression analysis was used to evaluate independent predictors of poor prognosis in BAD-stroke patients. Receiver-operating characteristic (ROC) analysis was used to estimate the predictive value of MPV and PC on BAD-stroke. Our research showed that a higher MPV (aOR, 2.926; 95% CI, 2.040-4.196; p<.001) and PC (aOR, 1.013; 95% CI, 1.005-1.020; p=.001) were independently associated with poor prognosis after adjustment for confounders. The ROC analysis of MPV for predicting poor prognosis showed that the sensitivity and specificity were 74% and 84.9%, respectively, and that the AUC was.843 (95% CI,.776-.909, p<.001). The optimal cut-off value was 12.35. The incidence of early neurological deterioration (END) was 24.5% (53 of 163), and 66% of patients in the poor prognosis group had END (33 of 50). Multiple logistic regression analyses showed that elevated MPV and PC were associated with the occurrence of END (p<.05). Our results suggested that an elevated MPV and PC may be important in predicting a worse outcome in BAD-stroke patients. Our study also demonstrated an independent association of MPV and PC with END, which is presumably the main reason for the poor prognosis.

The differential expression of AFF3 in cervical cancer and its correlation with clinicopathological features and prognosis

Background Cervical cancer (CC) is the second most common malignancy in women, and identifying biomarkers of CC is crucial for prognosis prediction. Here, we investigated the expression of AF4/FMR2 Family Member 3 (AFF3) in CC and its association with clinicopathological features and prognosis. Methods Tumour and adjacent tissues, along with clinicopathological features and follow-up information, were collected from 78 patients. AFF3 expression was assessed using quantitative real-time polymerase chain reaction and Western blotting. The correlation between AFF3 expression and CC symptoms was using chi-square test. The 5-year overall survival (OS) was analysed using the Kaplan-Meier method. The Univariate analysis of prognostic risk factors was conducted using the COX proportional hazards model, followed by multivariate COX regression analysis including variables with p < 0.01. Results AFF3 expression was downregulated in CC, and its levels were correlated with lymph node metastasis (LNM) and International Federation of Gynaecology and Obstetrics (FIGO) stage. Patients with low AFF3 expression had a lower 5-year OS rate (52.78%, 19/36). Postoperative survival was reduced in patients with histological grade 3 (G3), myometrial invasion (depth ≥ 1/2), lymphovascular space invasion, LNM, and advanced FIGO stage. Low expression of AFF3 (HR: 2.848, 95% CI: 1.144–7.090) and histological grade G3 (HR: 4.393, 95% CI: 1.663–11.607) were identified as independent prognostic risk factors in CC patients. Conclusion Low expression of AFF3 and histological G3 are independent predictors of poor prognosis in CC patients, suggesting that AFF3 could serve as a potential biomarker for prognostic assessment in CC.

Abstract 5220: Reduced expression of Glutathione peroxidase 2 (GPX2) is an independent predictor of poor prognosis in muscle-invasive urothelial carcinoma of the bladder

Abstract Background: The Glutathione peroxidase 2 (GPX2) is a selenium-dependent glutathione peroxidase with a pivotal role in removing potentially harming reactive oxygen species (ROS) from cells by catalyzing the reduction process of hydrogen peroxide to water. GPX2 is strongly expressed in normal urothelium but can be reduced in urothelial cancer. The aim of the study was to evaluate the potential clinical significance of GPX2 expression in urothelial bladder cancer. Design: GPX2 was analyzed by immunohistochemistry (IHC) in more than 2,500 urothelial bladder carcinomas in a tissue microarray format. Follow-up data were available for more than 600 patients with muscle-invasive disease. Results: GPX2 staining occurred in 67.5% of urothelial carcinomas including 11.4% with weak, 11.9% with moderate, and 44.2% with strong staining. While GPX2 staining was always strong in normal urothelium, it decreased markedly during grade and stage progression. Within pTa tumors, GPX2 positivity continuously decreased from pTaG2 low grade (99.4% positive) to pTa G2 high grade (97.2% positive) and to pTa G3 (90.5%; p=0.0013) while there was a marked further drop of GPX2 positivity from pTaG3 to muscle-invasive cancers (56.6%; p&amp;lt;0.0001 for pT2-4 vs. pTa G3). Within pT2-4 carcinomas, low or absent GPX2 staining was significantly linked to poor overall survival (p=0.0140), V1 (p&amp;lt;0.0001), L1 (p=0.0014), and high grade (p=0.0091), but statistically unrelated to pT and pN. In a multivariate analysis, the prognostic impact of reduced GPX2 expression (p=0.0081) was independent of pT (p&amp;lt;0.0001) and pN (p&amp;lt;0.0001) in pT2-4 tumors. GPX2 expression loss was inversely related to the expression of the luminal subtype markers GATA3 (p&amp;lt;0.0001), uroplakin 1b (p&amp;lt;0.0001) and cytokeratin 20 (p&amp;lt;0.0001) in pT2-4 carcinomas. Conclusion: GPX2 expression loss is a common event during bladder cancer progression which is strongly associated with poor prognosis in patients with pT2-4 urothelial carcinomas. GPX2 expression measurement - optimally together with other markers - could be useful for clinical risk assessment of bladder cancer patients. Citation Format: Henning Plage, Sebastian Hofbauer, Kira Furlano, Sarah Weinberger, Antonia Franz, Annika Fendler, Joachim Weischenfeldt, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Martina Kluth, Andreas H. Marx, Henrik Samtleben, Margit Fisch, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Stefan Koch, Nico Adamini, Ronald Simon, Guido Sauter, Henrik Zecha, Tobias Klatte, Sarah Minner, David Horst, Thorsten Schlomm, Michael Rink, Maximilian Lennartz. Reduced expression of Glutathione peroxidase 2 (GPX2) is an independent predictor of poor prognosis in muscle-invasive urothelial carcinoma of the bladder [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5220.

Association of lung immune prognostic index with survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

Lung immune prognostic index is based on derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. Lung immune prognostic index has reported association with survival outcomes in patients with various malignancies undergoing treatment with immune checkpoint inhibitors. However, the prognostic impact of pre-treatment lung immune prognostic index in patients with metastatic renal cell carcinoma receiving nivolumab plus ipilimumab treatment remains unclear. This study examines the association between lung immune prognostic index and outcomes in this setting. We retrospectively evaluated 156 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab at eight institutions. We assessed the associations between pre-treatment lung immune prognostic index and survival outcomes including progression-free survival, second progression-free survival (PFS2), cancer-specific survival and overall survival. Patients were classified into good (n=84, 54%), intermediate (n=52, 33%) and poor (n=20, 13%) lung immune prognostic index groups. Progression-free survival did not significantly differ between lung immune prognostic index groups, but there was significant difference in PFS2, cancer-specific survival and overall survival. In multivariable Cox proportional hazard analyses, high pre-treatment lung immune prognostic index was a significant predictor of poor PFS2 (vs. good group, intermediate group: P=0.01 and poor group: P=0.04) and poor overall survival (vs. good group, intermediate group: P=0.01 and poor group: P<0.01). Moreover, the patients with poor lung immune prognostic index had significantly poorer cancer-specific survival than those with good LIPI (P<0.01). High pre-treatment LIPI is suggested by our results to be a significant independent predictor of poor prognosis in patients receiving nivolumab plus ipilimumab for metastatic renal cell carcinoma.

Unveiling NUSAP1 as a common gene signature linking chronic HBV infection and HBV-related HCC

BackgroundHepatitis B virus (HBV) is a significant contributor to the development of hepatocellular carcinoma (HCC). Chronic HBV infection (CHB) facilitates disease progression through various mechanisms. However, the specific factor responsible for the progression of HBV infection to HCC remains unresolved. This study aims to identify the hub gene linking CHB and HBV-related HCC through bioinformatic analysis and experimental verification.MethodsDifferentially expressed genes (DEGs) were identified in datasets encompassing CHB and HBV-HCC patients from the GEO database. Enriched pathways were derived from GO and KEGG analysis. Hub genes were screened by protein–protein interaction (PPI) analysis and different modules in Cytoscape software. The significance of the selected hub gene in prognosis was further assessed in validated datasets. The effects of hub genes on cell growth and apoptosis were further determined in functional experiments.ResultsThe study revealed upregulation of NUSAP1 in CHBs and HBV-HCCs. High expression of NUSAP1 served as an independent predictor for poor prognosis of liver cancers. Functional experiments demonstrated that NUSAP1 promotes cell growth, influences cell cycle process, and protects cells from apoptosis in HepG2.2.15 cells.ConclusionNUSAP1 serves as a poor prognostic indicator for liver cancers, and potentially plays a crucial role in HBV-HCC progression by promoting proliferation and inhibiting apoptosis.

Prediction of Meningioma Grade Using Hematological Parameters

Predicting the aggressiveness of meningiomas may influence the surgical strategy timing. Because of the paucity of robust markers, the systemic immune-inflammation (SII) index is a novel biomarker to be an independent predictor of poor prognosis in various cancers including gliomas. We aimed to investigate the value of SII as well as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) indices in predicting prognosis. Records including demographic, clinical, and laboratory data of patients operated on due to intracranial meningioma in 2017-2023 were retrospectively reviewed. A total of 234 patients were included in this study. All of SII index, NLR, and PLR values at presentation were significantly higher in grade ≥2 meningiomas. A positive correlation was observed between SII index and Ki67 index (r=0.313; P<0.001); between NLR and Ki67 index (r=0.330; P<0.001); and between PLR and Ki67 index (r=0.223; P<0.01). SII index (optimal cutoff level >618), NLR (optimal cutoff level >3.53), and PLR (optimal cutoff level >121.2) showed significant predictive values. This is the first study to assess the prognostic value of the SII index in patients with intracranial meningiomas. Increased SII index, NLR and PLR were correlated with higher grade and higher Ki-67 index. They also harbor the potential to screen patients that may need more aggressive treatments or more frequent follow-up examinations.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8months. The median PFS was 10.0months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Bioinformatic analysis reveals prognostic value and immunotherapy potential of Siglec-15 in laryngeal squamous cell carcinoma

BackgroundLaryngeal squamous cell carcinoma (LSCC) is the ultimate common malignant head and neck cancer with dismal prognosis. The expression pattern and clinical significance of Siglec-15 (Sialic acid-binding immunoglobulin-like lectin 15) in LSCC are poorly understood. In order to lay the groundwork for future immune-related research on Siglec-15 in LSCC, we set out to study its expression and prognostic importance in the disease, as well as to use bioinformatics to investigate the immune features modulated by Siglec-15 in LSCC. Methods① In order to get the gene expression profile and clinical data for TCGA head and neck cancer (TCGA-HNSC), you may access the relevant data from UCSC xena and use 110 cases of laryngeal cancer as a training set. Two datasets, GSE27020 and GSE25727, were obtained from the GEO databank and utilized as validation sets. These datasets include expression profiles and clinical information. The Siglec-15 gene and immune characteristics were analyzed by bioinformatics methods. ② Retrospectively collected routine paraffin specimens from patients with pathological diagnosis of squamous cell carcinoma from December 2012 to November 2015 in Sun Yat-sen Memorial Hospital and fresh frozen tissue of patients from June 2021 to March 2022. Immunohistochemistry method, immunofluorescence technique and real-time quantitative PCR was used to examine the difference of Siglec-15 appearance in LSCC tissue and adjacent tissue, and its correlation of prognosis, clinic pathological characteristics and CD8+T lymphocyte infiltration. Using human laryngeal cancer cell line (LCC), we studied the influence of Siglec-15 in cell proliferation and invasion. ResultsWe identified Siglec-15 was upregulated in LSCC. The patients in Siglec-15 high expression group had a poor overall survival (OS) based on the clinical information from TGCA and 111 LSCC patients that hospitalized in Sun Yat-sen Memorial Hospital. The COX regression analysis indicated Siglec-15 as an independent predictor for poor prognosis of LSCC. Bioinformatic analysis suggested that the high expression of Siglec-15 shape an immune suppressive tumor microenvironment (TEM), leading to poor response to immunotherapy in LSCC. Siglec-15 enhanced cell invasion and proliferation, as we showed in vitro. ConclusionOur study support Siglec-15 as a potential predictor for LSCC prognosis and an attractive target for LSCC immunotherapy.

1q21+ is associated with poor prognosis in newly diagnosed multiple myeloma patients with extramedullary disease: a retrospective study.

1q21+ is a common cytogenetic abnormality in multiple myeloma (MM) and is considered an independent predictor of poor prognosis; however, its impact on extramedullary disease (EMD) remains unknown. Our study reviewed the clinical relevance and prognostic value of 1q21+ status in 92 patients with NDMM and EMD. 1q21+ was detected in 23.9% (22/92) of patients. Patients with 1q21+ presented with advanced International Staging System stages (P = 0.006), lower level of hemoglobin (P = 0.004), higher percentage of plasma cells in the bone marrow (P < 0.001), higher level of serum β2-microglobulin (7.24g/L vs. 3.85g/L, P = 0.003), and higher levels of lactic dehydrogenase (LDH) (206.5 U/L vs. 177 U/L, P = 0.019). The prevalence of soft tissue-related EMD (EMD-S) (54.5% vs. 18.6%, P < 0.001), renal dysfunction (50.5% vs. 17.7%, P = 0.002), and hypercalcemia (27.3% vs. 7.1%, P = 0.011) was also higher. 1q21+ was strongly associated with other high-risk cytogenetic abnormalities, including IgH/FGFR3 (22.7% vs. 4.3%, P = 0.007) and IgH/MAF translocations (22.7% vs. 1.4%, P < 0.001). 1q21+ patients had significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: 24months vs. 47months, P = 0.002; PFS: 14months vs. 38months, P < 0.001); the poor survival outcomes could not be reversed by autologous hematopoietic stem cell transplantation. Multivariate analysis suggested that 1q21+ , EMD-S, elevated lactate dehydrogenase (LDH) levels, and P53 deletion were independent risk factors for poor prognosis in patients with EMD. In patients with 1q21+ EMD, hypercalcemia, elevated LDH levels, and P53 deletion were independent adverse risk prognostic factors.

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients

BackgroundRoutine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP).MethodsData from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging.ResultsPreoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages.ConclusionThe PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

A retrospective analysis of prognostic factors and treatment choices in small cell lung cancer with liver metastasis.

Small cell lung cancer (SCLC) is characterized by high aggressiveness and early dissemination, with the liver being the most common site of metastasis. Although it has been established that the prognosis for SCLC with liver metastasis is exceedingly poor, comprehensive data on clinical features, prognostic factors, treatment options, and outcomes of this patient population remain limited. This retrospective study aims to examine the clinicopathological features and current treatment landscape and to identify prognostic factors associated with SCLC with liver metastasis in real-world settings. We conducted a retrospective analysis of data on SCLC patients with liver metastasis at initial diagnosis between January 1, 2013, and January 1, 2022. Kaplan-Meier analysis and log-rank tests were employed to estimate the overall survival (OS) and progression-free survival (PFS). Cox regression models were utilized to identify independent prognostic factors. A total of 349 patients were included in the study, with 97.7% of patients exhibiting pure SCLC and 42.4% of patients presenting with concomitant bone metastasis. Approximately one-fourth of the patients had metastases in ≥3 organs, and 18.9% of patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. The median OS was 10.97 months (95% CI: 9.88-12.06) for those who received first-line therapy (n=286). Of these, 263 patients were treated with chemotherapy, showing a median OS of 11.37 months. Furthermore, 43.8% of patients received second-line treatment, and 81 patients proceeded to third-line treatment. ECOG PS ≥2 and mixed-SCLC were identified as independent adverse prognostic factors in SCLC with liver metastasis, whereas treatments including systemic treatment alone or in combination with local radiotherapy were associated with better prognoses. This retrospective study substantiated that ECOG PS ≥2 and mixed SCLC are independent predictors of poor prognosis for SCLC with liver metastasis. Additionally, different treatment strategies can improve the survival of this patient population, with chemotherapy currently being the main treatment option.

Identification of P3H1 as a Predictive Prognostic Biomarker for Bladder Urothelial Carcinoma Based on the Cancer Genome Atlas Database.

The extracellular matrix in the tumor microenvironment are closely related to the development of tumors. This study's primary aim is to study the association between prolyl 3-hydroxylase 1 (P3H1) which mainly expresses collagen in extracellular matrix and the progression and prognosis of bladder cancer (BC). The clinical and transcriptome data were acquired from the cancer genome atlas database. BLCAsubtyping is used to evaluate tissue subtypes of BC. The COX proportional hazards can be used to evaluate the survival process's influencing factors. Immunohistochemistry was used to identify differences in the expression of P3H1 in cancer and paired adjacent tissues. GSEA was used to investigate the underlying biological processes. Finally, ssGSEA, TIMER and pRRophetic were used to study the relationship between P3H1 and immune cell infiltration and drug sensitivity. The expression of P3H1 was substantially higher in highly invasive BC samples than in low invasive BC. P3H1 was an independent predictor of overall survival (HR = 1.12, p = 0.03). P3H1 expression was significantly higher in tumor tissues than adjacent normal tissues in clinical tissue samples, and was significantly higher in highly stage cancer than low stage cancer samples. Samples with high P3H1 expression had a higher level of immune cell infiltration and immune function, as well as a significant correlation with macrophage and dendritic cell infiltration and TGF-beta, Th1 cells, and macrophage regulation (cor >0.3, p <0.05). P3H1 high expression samples were substantially more sensitive to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medicines than P3H1 low expression samples. P3H1 is a possible oncogene and an independent predictor of poor prognosis in BC; it also has enhanced sensitivity to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medications.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites(log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

Prognostic Effect of Preoperative Inflammatory Markers on Morbidity and Overall Survival in Pancreatic Adenocarsinoma.

His study aimed to evaluate the availability of common diagnostic tests and biochemical markers in predicting poor prognosis in patients with pancreatic adenocarcinoma (PAC). The primary outcome measure was to identify predictive prognostic factors. The secondary outcome measure was to compare predictive measures in patients who survived or did not survive in the follow-up period. Medical data of 51 patients were obtained who underwent resection surgery for PAC between January 2016 and May 2022. There were two groups according to the mortality in the follow-up period group general mortality positive (GMP; n = 29) and group general mortality negative (GMN; n = 22). Stage IIb was the most common stage in subgroups. Preoperative diagnostic tests revealed that aspartate aminotransferase (AST) level, De Ritis ratio (DRR), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), immature granulocyte (IG) count, and IG ratio (IG%) are higher, and hemoglobin (Hgb) levels are lower in the GMP group (P < 0.05). In univariate analysis, seven variables, including AST ≥20.5 (P = 0.001), DRR ≥1.05 (P ≤ 0.001), CEA ≥3.32 (P = 0.02), IG count ≥0.06 (P < 0.01), Hgb ≤11.75 (P = 0.01), poor differentiation (P < 0.001) and existence of life-threatening complication (P < 0.01) were identified. In multivariate analysis, only DRR (≥1.05;100% specificity and 72% sensitivity) and poor differentiation (P = 0.019) were found to be independent prognostic factors for overall survival. The median overall survival of patients with the DRR ≥1.05 and poor tumor differentiation was lower, and the mortality rate was higher than the patients with DRR and without poor tumor differentiation (10.65 ± 3.11 months vs. 61.86 ± 5.36 months and 100% vs. 26.7%, P < 0.001). Pretreatment high DRR, high IG counts and IG%, and poor differentiation of the tumor might be used as independent predictors of poor prognosis and mortality in patients with PAC.

Ratio of Circulating CD8 + T Lymphocytes to M-MDSCs (CD8MMR): A Novel Prognostic Predictor for Treatment-Naïve DLBCL Patients

Introduction: CD8 + T lymphocytes are crucial in contemporary cell-and-immunotherapies as they can be functionally enhanced or manipulated. Monocytic myeloid-derived suppressor cells (M-MDSCs) are known for their intense immunosuppressive ability, and higher percentages of circulating M-MDSCs among peripheral-blood monocytes or white cells are associated with a worse prognosis. Recently, a low lymphocyte-to-monocyte ratio (LMR) has been linked to a poor prognosis in lymphoma patients. Consequently, we hypothesized that the ratio of circulating CD8 + T lymphocytes to M-MDSCs (CD8MMR) could be a novel and more precise predictor for the clinical outcomes of DLBCL patients before initiating treatment. Methods: This prospective, observational study enrolled 136 adults with treatment-naïve DLBCL from May 2019 to March 2023 in a tertiary medical center in Taiwan. Patients with primary CNS lymphoma or primary mediastinal B-cell lymphoma were excluded. Fresh peripheral blood samples were obtained to calculate the absolute counts of CD8 + T lymphocytes and M-MDSCs, defined as alive singlets with CD45 + CD3 + CD8 + and CD45 + CD15 - CD14 + CD11b + CD33 + HLA-DR low/- by flow cytometry, respectively. ROC analysis and AUC determined the cut-off values for LMR and CD8MMR. Results: For 136 treatment-naïve DLBCL patients, the median age was 70, with 61.8% being male. Among them, 37.5% were in stage IV, and 27.9% were classified as the germinal-center B-cell (GCB) subtype by IHC staining according to the Hans algorithm. Additionally, 43.4% were diagnosed with double expressor lymphoma (DEL). The IPI risk score distribution was as follows: 7.4%, 18.4%, 17.6%, 24.3%, 19.9%, and 12.5% were in scores 0, 1, 2, 3, 4, and 5, respectively. Of note, the median level of LMR was 2.17, the median level of absolute counts of circulating CD8 + T lymphocytes was 385/µL, the median level of absolute counts of circulating M-MDSCs was 102/µL, and the median level of CD8MMR was 3.56. DLBCL patients with high-risk IPI had a significantly lower CD8MMR than patients with intermediate or low-risk IPI (1.34 vs. 4.51 vs. 7.82, PH vs. L = 0.001, PH vs. I = 0.060, PI vs. L = 0.082). DLBCL patients with the non-GCB subtype (2.75 vs. 5.63, P = 0.031) also demonstrated a significantly lower CD8MMR. Additionally, there were trends of lower CD8MMR in elderly patients &amp;gt; 70 (2.74 vs. 3.91, P = 0.209) and patients with DEL (3.33 vs. 4.65, P = 0.101). After a median follow-up of 22.6 months for the 136 DLBCL patients, LMR was at first tested, and patients with LMR &amp;lt; 1.19 had significantly worse PFS (13.8 months vs. non-reach, Log Rank P = 0.004) and OS (non-reach vs. non-reach, Log Rank P = 0.019) than those with LMR ≥ 1.19. Next, we examined the CD8MMR, and patients with CD8MMR &amp;lt; 4.40 experienced significantly worse PFS (21.3 months vs. non-reach, Log Rank P &amp;lt; 0.001) and OS (non-reach vs. non-reach, Log Rank P &amp;lt; 0.001) compared to those with CD8MMR ≥ 4.40 [Figure]. We subsequently conducted a multivariate Cox regression analysis to validate whether CD8MMR &amp;lt; 4.40 could serve as an independent predictor of poor prognosis [Table]. The results showed that “CD8MMR &amp;lt; 4.40” was confirmed as an independent prognostic factor for both PFS (HR = 2.747; 95% CI = 1.275 to 5.918; P = 0.010) and OS (HR = 3.669; 95% CI = 1.462 to 9.211; P = 0.006) after adjusting for confounding factors, including age, sex, IPI risk scores, bulky mass &amp;gt; 10 cm, non-GCB type, DEL, and LMR &amp;lt; 1.19. In this study cohort, 106 (77.9%) patients received R-CHOP-like regimens as induction therapies, 25 (18.4%) patients received an R-EPOCH regimen, two (1.5%) patients received an R-HyperCVAD regimen, and three (2.2%) patients died before completing the first cycle of chemoimmunotherapy. Among the 106 DLBCL patients receiving R-CHOP-like regimens, 57 patients showed CD8MMR &amp;lt; 4.40 and reported a significantly lower rate of complete remission (73.7% vs. 95.9%, P = 0.006) at the end of induction therapy compared to the 49 patients with CD8MMR ≥ 4.40. Furthermore, patients with CD8MMR &amp;lt; 4.40 had significantly worse PFS (17.4 months vs. non-reach, P &amp;lt; 0.001) and OS (non-reach vs. non-reach, P &amp;lt; 0.001) compared to those with CD8MMR ≥ 4.40. Conclusion: A low ratio of circulating CD8 + T lymphocytes to M-MDSCs (CD8MMR) serves as a poor prognostic factor for both PFS and OS in treatment-naïve DLBCL patients. This finding warrants further investigation and highlights the possibility of risk-adapted strategies when treating DLBCL patients.