Independent Predictor Of Poor Prognosis Research Articles

The immunological landscape and silico analysis of key paraptosis regulator LPAR1 in gastric cancer patients

This study aims to identify key regulators of paraptosis in gastric cancer (GC) and explore their potential in guiding therapeutic strategies, especially in stomach adenocarcinoma (STAD). Genes associated with paraptosis were identified from the references and subjected to Cox regression analysis in the TCGA-STAD cohort. Using machine learning models, LPAR1 consistently ranked highest in feature importance. Multiple sequencing data showed that LPAR1 was significantly overexpressed in cancer-associated fibroblasts (CAFs). LPAR1 expression was significantly higher in normal tissues, and ROC analysis demonstrated its discriminative ability. Copy number alterations and microsatellite instability were significantly associated with LPAR1 expression. High LPAR1 expression correlated with advanced tumor grades and specific cancer immune subtypes, and multivariate analysis confirmed LPAR1 as an independent predictor of poor prognosis. LPAR1 expression was associated with different immune response metrics, including immune effector activation and upregulated chemokine secretion. High LPAR1 expression also correlated with increased sensitivity to compounds, such as BET bromodomain inhibitors I-BET151 and RITA, suggesting LPAR1 as a biomarker for predicting drug activity. FOXP2 showed a strong positive correlation with LPAR1 transcriptional regulation, while increased methylation of LPAR1 promoter regions was negatively correlated with gene expression. Knockdown of LPAR1 affected cell growth in most tumor cell lines, and in vitro experiments demonstrated that LPAR1 influenced extracellular matrix (ECM) contraction and cell viability in the paraptosis of CAFs. These findings suggest that LPAR1 is a critical regulator of paraptosis in GC and a potential biomarker for drug sensitivity and immunotherapy response. This underscores the role of CAFs in mediating tumorigenic effects and suggests that targeting LPAR1 could be a promising strategy for precision medicine in GC.

TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.

Long Non-Coding H19 in Lymphocytes: Prognostic Value in Acute Ischemic Stroke Patients.

Acute ischemic stroke (AIS) is a cerebrovascular disease that seriously affects the physical and mental health and quality of life of patients. However, there is a lack of reliable prognostic prediction methods. The main objective of this study was to investigate the prognostic value of long non-coding RNA (lncRNA) H19 in lymphocytes of patients with AIS, and to construct a prognostic prediction model for AIS including lncRNA H19 in lymphocytes, which would provide new ideas for the prognostic evaluation of AIS. Poor prognosis was defined when the patient's modified Rankin scale (mRS) score at 3 months after AIS onset was greater than 2. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the level of lncRNA H19 in lymphocytes. Spearman correlation analysis revealed a positive correlation between lncRNA H19 and mRS score at 3 months after AIS onset (r = 0.1977, p = 0.0032), while lncRNA H19 was negatively correlated with white blood cells counts, lymphocytes counts, and neutrophils counts. Logistic regression analysis identified lncRNA H19 as an independent predictor of poor prognosis (OR = 3.062 [1.69-5.548], p < 0.001). Moreover, a nomogram prediction model incorporating lncRNA H19 in lymphocytes demonstrated effective discrimination, calibration, and clinical applicability in predicting AIS outcomes. The findings suggest that lncRNA H19 in lymphocytes could be a valuable prognostic indicator and a potential pharmacological target for AIS patients, and might be a novel pathway for enhanced prognostic evaluation and targeted therapeutic strategies.

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.

Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.

Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism. To determine whether this mechanism broadly impacts diabetic complications, we investigated the role of ARRDC4 in the pathogenesis of diabetic cardiac/skeletal myopathy using cellular and animal models. High glucose promoted translocation of MondoA into the nucleus, which upregulated Arrdc4 transcriptional expression, increased lysosomal GLUT1 trafficking, and blocked glucose transport in cardiomyocytes, forming a feedback mechanism. This role of ARRDC4 was confirmed in human muscular cells from type 2 diabetic patients. Prolonged hyperglycemia upregulated myocardial Arrdc4 expression in multiple types of mouse models of diabetes. We analyzed hyperglycemia-induced cardiac and skeletal muscle abnormalities in insulin-deficient mice. Hyperglycemia increased advanced glycation end-products and elicited oxidative and endoplasmic reticulum stress leading to apoptosis in the heart and peripheral muscle. Deletion of Arrdc4 augmented tissue glucose transport and mitochondrial respiration, protecting the heart and muscle from tissue damage. Stress hemodynamic analysis and treadmill exhaustion test uncovered that Arrdc4-knockout mice had greater cardiac inotropic/chronotropic reserve with higher exercise endurance than wild-type animals under diabetes. While multiple organs were involved in the mechanism, cardiac-specific overexpression using an adenoassociated virus suggests that high levels of myocardial ARRDC4 have the potential to contribute to exercise intolerance by interfering with cardiac metabolism through its interaction with GLUT1 in diabetes. Importantly, the ARRDC4 mutation mouse line exhibited greater exercise tolerance, showing the potential therapeutic impact on diabetic cardiomyopathy by disrupting the interaction between ARRDC4 and GLUT1. ARRDC4 regulates hyperglycemia-induced toxicities toward cardiac and skeletal muscle, revealing a new molecular framework that connects hyperglycemia to cardiac/skeletal myopathy to exercise intolerance.

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.

Tumor-Intrinsic Perinuclear LOXL2: Prognostic Relevance and Relationship with YAP1 Activation Status in Oral Squamous Cell Carcinoma.

Lysyl oxidase-like 2 (LOXL2) expression and function is frequently altered in different cancers but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%) and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates, and perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation. Patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.

Association of potentially inappropriate medications with prognosis among older patients with non-small cell lung cancer

BackgroundPotentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC.MethodsIn this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS).ResultsWe finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P < 0.001). Baseline PIM use and PIM after systemic therapy were significantly associated with inferior OS (476 days vs. 844 days, P = 0.044; and 633 days vs. 1600 days, P = 0.007; respectively). In multivariable analysis, both baseline PIM use and PIM after systemic therapy were independent predictors of poor prognosis (adjusted HR, 1.33; 95% CI, 1.01–1.75; P = 0.041; and adjusted HR, 1.86; 95% CI, 1.11–3.14; P = 0.020; respectively).ConclusionsPIMs are prevalent among older patients with NSCLC and are independent predictors of NSCLC prognosis. There is an urgent need for clinicians to conduct medication reconciliation and appropriate deprescribing for this population, especially for patients with multiple PIMs.

Association of surgical margin on prognosis after hepatectomy for colorectal cancer liver metastases with RAS mutations

BackgroundAlthough outcomes of treatment for colorectal cancer liver metastases (CRLM) have improved with multidisciplinary treatment, recurrence rates after resection of liver metastases are still high. Although surgical margin (SM) is considered irrelevant in the case of R0 resection, its effectiveness is still unclear. In this study, we investigated the prognostic association of SM in CRLM according to RAS status. MethodsOf 220 patients who had undergone initial hepatic resection for CRLM at our hospital between January 2000 and February 2020, finally, 164 remained in the study cohort. SMs (mms) were measured by macroscopic and microscopic examinations. Associations between SM, presence or absence of RAS mutations, and prognosis were analyzed using multivariate analysis with the Cox proportional hazards model. ResultsOf the 164 patients, 68 (41 %) had RAS mutations. The RAS mutation group had significantly poorer disease-free survival (DFS) (P < 0.001) and over-all survival (OS) (P < 0.001). In the RAS wild group, SM status was not significantly associated with OS or DFS, whereas in the RAS mutation group, SM< 2 mm was significantly associated with worse DFS (P = 0.014). Multivariate analysis showed that SM< 2 mm was an independent predictor of poor DFS in the RAS mutation group (HR 21.3, 95 % CI: 2.25–201.3, P = 0.008). ConclusionsRAS mutation status is an independent predictor of poor prognosis after hepatectomy for CRLM. Especially in patients with RAS mutations, SM < 2 mm is associated with significantly worse post-hepatectomy DFS, suggesting achieving a wide SM (≥2 mm) is indicated in patients with RAS mutations SynopsisRAS mutation is an independent predictor of poor prognosis after hepatectomy for CRLM. Especially in patients with RAS mutations, SM < 2 mm is associated with significantly worse post-hepatectomy DFS, suggesting achieving a wide SM (≥2 mm) is indicated.

A Clinical Model predicting the 90-Day Prognosis after Mechanical Thrombectomy in Patients with Acute Ischemic Stroke: A Retrospective Study.

Mechanical thrombectomy (MT) is usually recommended for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) within the time window (6 hours after the disease onset). However, poor prognosis in acute great vascular occlusive stroke after MT, which is not an uncommon occurrence, can be attributed to an absence of appropriate postoperative monitoring. Transcranial Doppler (TCD) ultrasound and quantitative electroencephalography (QEEG) offer the advantages of fast, convenient, and bedside examinations compared with conventional imaging techniques. We aimed to analyze the predictive performance of clinical factors, Transcranial Doppler (TCD) ultrasound and quantitative electroencephalography (QEEG) for the prognosis of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) at 90 days after discharge. Patients achieved revascularization through MT performed within 6 hours after the onset of AIS due to LVO were included. We use the data to build four predictive models of prognosis and compared the predictive performance measured by the area under the curve, sensitivity, and specificity. A total of 74 patients were included in the study. Among them, 47 patients had a poor prognosis (63.5%) on discharge, and 45 patients had a poor prognosis (60.8%) at 90 days after discharge. Independent predictors of poor prognosis at 90 days after discharge were identified as follows: age, NIHSS score on admission, PI on the affected/healthy side, and RAP. Among the four models built, AUC was the highest (reaching 0.831) when age was combined with NIHSS score on admission, TCD parameters (VD on the affected side, PI on the affected/healthy side), and QEEG parameter (RAP) for prognostic prediction. However, AUC of the four predictive models did not differ significantly (P>0.05). Age, NIHSS score on admission, TCD parameters, and QEEG parameter were independent predictors of the prognosis at 90 days after discharge in patients receiving MT for AIS due to LVO in the anterior circulation. The model combining the above four parameters may be helpful for prognostic prediction in such patients.

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.