scholarly journals A Novel Apoptosis-Related Gene Signature Predicts Biochemical Recurrence of Localized Prostate Cancer After Radical Prostatectomy

2020 ◽  
Vol 11 ◽  
Author(s):  
Qijie Zhang ◽  
Kai Zhao ◽  
Lebin Song ◽  
Chengjian Ji ◽  
Rong Cong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factor ◽  
Biochemical Recurrence ◽  
Prognostic Value ◽  
Gene Signature ◽  
Clinical Parameters ◽  
Related Gene ◽  
Qrt Pcr ◽  
Validation Set ◽  
Apoptosis Related Gene

Background: Nowadays, predictions of biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) are mainly based on clinical parameters with a low predictive accuracy. Given the critical role of apoptosis in PCa occurrence and progression, we aimed to establish a novel predictive model based on apoptosis-related gene signature and clinicopathological parameters that can improve risk stratification for BCR and assist in clinical decision-making.Methods: Expression data and corresponding clinical information were obtained from four public cohorts, one from The Cancer Genome Atlas (TCGA) dataset and three from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis (WGCNA) was performed to identify candidate modules closely correlated to BCR, and univariate and multivariate Cox regression analyses were utilized to build the gene signature. Time-dependent receiver operating curve (ROC) and Kaplan–Meier (KM) survival analysis were used to assess the prognostic value. Finally, we analyzed the expression of genes in the signature and validated the results using quantitative real-time PCR (qRT-PCR).Results: The novel gene signature we established exhibited a high prognostic value and was able to act as an independent risk factor for BCR [Training set: P < 0.001, hazard ratio (HR) = 7.826; Validation set I: P = 0.006, HR = 2.655; Validation set II: P = 0.003, HR = 4.175; Validation set III: P < 0.001, HR = 3.008]. Nomogram based on the gene signature and clinical parameters was capable of distinguishing high-risk BCR patients. Additionally, functional enrichment analysis showed several enriched pathways and biological processes, which might help reveal the underlying mechanism. The expression results of qRT-PCR were consistent with TCGA results.Conclusion: The apoptosis-related gene signature could serve as a powerful predictor and risk factor for BCR in localized PCa patients after RP.

scholarly journals Construction and Validation of a Robust Cancer Stem Cell-Associated Gene Set-Based Signature to Predict Early Biochemical Recurrence in Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Bide Liu ◽  
Xun Li ◽  
Jiuzhi Li ◽  
Hongyong Jin ◽  
Hongliang Jia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
High Risk ◽  
Cancer Stem Cell ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Gene Set ◽  
Validation Set

Background. Postoperative early biochemical recurrence (BCR) was an essential indicator for recurrence and distant metastasis of prostate cancer (PCa). The aim of this study was to construct a cancer stem cell- (CSC-) associated gene set-based signature to identify a subgroup of PCa patients who are at high risk of early BCR. Methods. The PCa dataset from The Cancer Genome Atlas (TCGA) was randomly separated into discovery and validation set. Patients in discovery set were divided into early BCR group and long-term survival group. Propensity score matching analysis and differentially expressed gene selection were used to identify candidate CSC-associated genes. The LASSO Cox regression model was finally performed to filter the most useful prognostic CSC-associated genes for predicting early BCR. Results. By applying the LASSO Cox regression model, we built a thirteen-CSC-associated gene-based early BCR-predicting signature. In the discovery set, patients in high-risk group showed significantly poorer BCR free survival than that patients in low-risk group (HR: 4.91, 95% CI: 2.75–8.76, P < 0.001 ). The results were further validated in the internal validation set (HR: 2.99, 95% CI: 1.34–6.70, P = 0.005 ). Time-dependent ROC at 1 year suggested that the CSC gene signature ( AUC = 0.800 ) possessed better predictive value than any other clinicopathological features in the entire TCGA cohort. Additionally, survival decision curve analysis revealed a considerable clinical usefulness of the CSC gene signature. Conclusions. We successfully developed a CSC-associated gene set-based signature that can accurately predict early BCR in PCa cancer.

scholarly journals Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review

2019 ◽  
Vol 75 (6) ◽  
pp. 967-987 ◽  
Author(s):  
Thomas Van den Broeck ◽  
Roderick C.N. van den Bergh ◽  
Nicolas Arfi ◽  
Tobias Gross ◽  
Lisa Moris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Biochemical Recurrence ◽  
Prognostic Value ◽  
Curative Intent

scholarly journals Prognostic value of morphologic and clinical parameters in pT2 - pT3 prostate cancer

2007 ◽  
Vol 33 (5) ◽  
pp. 662-672 ◽  
Author(s):  
Jose C. Almeida ◽  
Raissa P. Menezes ◽  
Selma A. Kuckelhaus ◽  
Anamelia L. Bocca ◽  
Florencio Figueiredo
Keyword(s):  
Prostate Cancer ◽  
Prognostic Value ◽  
Clinical Parameters

scholarly journals A Novel Ferroptosis-Related Gene Signature Robustly Predicts Clinical Prognosis And Tumor Immunity in Patients With Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Wei Song ◽  
Weiting Kang ◽  
Qi Zhang
Keyword(s):  
High Risk ◽  
Clear Cell ◽  
Risk Group ◽  
Gene Signature ◽  
Renal Clear Cell Carcinoma ◽  
High Risk Group ◽  
Risk Scores ◽  
Related Gene ◽  
Clinical Prognosis ◽  
Validation Set

Abstract Objective: This study aimed to construct a ferroptosis-related gene signature to predict clinical prognosis and tumor immunity in patients with kidney renal clear cell carcinoma (KIRC).Methods: The mRNA expression profiles and corresponding clinical data of KIRC patients were downloaded from The Cancer Genome Atlas (TCGA), which were randomly divided into training (398 patients) and validation set (132 patients). The iron death related (IDR) prediction model was constructed based on training set and 60 ferroptosis-related genes from previous literatures, followed by prognostic performance evaluation and verification using the validation set. Moreover, functional enrichment, immune cell infiltration, metagene clusters correlation, and TIDE scoring analyses were performed. Results: In total, 23 ferroptosis-related genes were significantly associated with overall survival (OS). The IDR prediction model (a 10-gene signature) was then constructed to stratify patients into two risk groups. The OS of KIRC patients with high-risk scores was significantly shorter than those with low-risk scores. Moreover, the risk score was confirmed as an independent prognostic predictor for OS. The positive and negative correlated genes with this model were significantly enriched in p53 signaling pathway, and cGMP-PKG signaling pathway. The patients in the high-risk group had higher ratios of plasma cells, T cells CD8, and T cells regulatory Tregs. Furthermore, IgG, HCK, LCK, and Interferson metagenes were significantly correlated with risk score. By TIDE score analysis, patients in the high-risk group could benefit from immunotherapy.Conclusions: The identified ferroptosis-related gene signature is significantly correlated with clinical prognosis and immune immunity in KIRC patients.

scholarly journals ETS-related gene(ERG) expression as a predictor of oncological outcomes in patients with high-grade prostate cancer treated with primary androgen deprivation therapy: a cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025161
Author(s):  
Mark Rezk ◽  
Ashish Chandra ◽  
Daniel Addis ◽  
Henrik Møller ◽  
Mina Youssef ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cohort Study ◽  
Prostate Specific Antigen ◽  
Outcome Measures ◽  
Androgen Deprivation Therapy ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Related Gene

ObjectivesTo determine whetherETS-related gene(ERG) expression can be used as a biomarker to predict biochemical recurrence and prostate cancer-specific death in patients with high Gleason grade prostate cancer treated with androgen deprivation therapy (ADT) as monotherapy.MethodsA multicentre retrospective cohort study identifying 149 patients treated with primary ADT for metastatic or non-metastatic prostate cancer with Gleason score 8–10 between 1999 and 2006. Patients planned for adjuvant radiotherapy at diagnosis were excluded. Age at diagnosis, ethnicity, prostate-specific antigen and Charlson-comorbidity score were recorded. Prostatic tissue acquired at biopsy or transurethral resection surgery was assessed for immunohistochemical expression ofERG. Failure of ADT defined as prostate specific antigen nadir +2. Vital status and death certification data determined using the UK National Cancer Registry. Primary outcome measures were overall survival (OS) and prostate cancer specific survival (CSS). Secondary outcome was biochemical recurrence-free survival (BRFS).ResultsThe median OS of our cohort was 60.2 months (CI 52.0 to 68.3).ERGexpression observed in 51/149 cases (34%). Multivariate Cox proportional hazards analysis showed no significant association betweenERGexpression and OS (p=0.41), CSS (p=0.92) and BRFS (p=0.31). Cox regression analysis showed Gleason score (p=0.003) and metastatic status (p<1×10-5) to be the only significant predictors of prostate CSS.ConclusionsNo significant association was found betweenERGstatus and any of our outcome measures. Despite a limited sample size, our results suggest thatERGdoes not appear to be a useful biomarker in predicting response to ADT in patients with high risk prostate cancer.

Association of neuroendocrine (NE) mRNA expression profiling in hormone-sensitive tumors samples with adverse clinical outcome in castration-resistant prostate cancer (CRPC) patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 165-165
Author(s):  
Mayra Orrillo ◽  
Natalia Jimenez ◽  
Oscar Reig ◽  
Giancarlo Castellano ◽  
Albert Font ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcome ◽  
Treatment Strategies ◽  
Gene Signature ◽  
Molecular Profile ◽  
Castration Resistant Prostate Cancer ◽  
Adverse Clinical Outcome ◽  
Related Gene ◽  
Primary Tumors ◽  
Hormone Sensitive

165 Background: NE dedifferentiation is associated to clinical aggressiveness and resistance to androgen receptor inhibition in prostate cancer. We investigated impact of a NE expression signature in the clinical outcome of mCRPC patients treated with taxanes. Methods: This is a multicenter retrospective study. A customized panel of 45 NE-related gene signature was tested in total RNA from formalin-fixed paraffin-embedded hormone-sensitive tumor samples, by the nCounter platform (Nanostring Technologies). Patients were grouped according to their molecular profile by unsupervised clustering. Expression levels were correlated with taxanes response and clinical outcome. Independent association with survival was evaluated by multivariate Cox modeling. Results: Eighty seven patients were included in the study, 79 were treated with docetaxel and 8 with cabazitaxel. Median age was 64.8 (44-88.3) years and median follow-up was 20.7 (1.17-74.4) months. High expression of the NE signature was associated with a shorter time of CRPC development (N=60, median 12.8 vs 21.6, HR 2.4, 95%CI 1.3-4.3, P=0.003) and shorter OS from CRPC diagnosis (median 24.1 vs 41.33, HR 2.3, 95%CI 1.4-3.8, P=0.001). Moreover, according to the outcome to taxanes, high NE signature correlated with lower PSA-PFS (median 6.6 vs 10.1 mo P=0.047, HR 1.6, 95%CI 1-2.7, P=0.05) and OS (median 19 vs 22 mo, HR 1.8, 95%CI 1.1-2.8, P=0.014), and it was independently associated to a lower OS (HR 1.9, 95%CI 1.1-3.2, P=0.016). Conclusions: NE-related gene expression in hormone-sensitive tumor samples is associated with adverse clinical outcome and lower taxane benefit in metastatic CRPC patients. Thus, molecular characterization of primary tumors may be useful to guide treatment strategies in metastatic prostate cancer.

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