Dataset Information

Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages.

ABSTRACT: Prostate cancer (PC) is one of the most common cancers among men worldwide, and advanced PCs, such as locally advanced PC (LAPC) and castration-resistant PC (CRPC), present the greatest challenges in clinical management. Current indicators have limited capacity to predict the disease course; therefore, better prognostic markers are greatly needed. In this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets, including RNA-Seq data from the prostate adenocarcinoma (PRAD; n = 55) and West Coast Dream Team - metastatic CRPC (WCDT-MCRPC; n = 84) projects, to evaluate the transcriptome changes associated with progression-free survival (PFS) for LAPC and CRPC, respectively. We identified the genes whose expression was positively/negatively correlated with PFS. In LAPC, the genes with the most significant negative correlations were ZC2HC1A, SQLE, and KIF11, and the genes with the most significant positive correlations were SOD3, LRRC26, MIR22HG, MEG3, and MIR29B2CHG. In CRPC, the most significant positive correlations were found for BET1, CTAGE5, IFNGR1, and GIMAP6, and the most significant negative correlations were found for CLPB, PRPF19, ZNF610, MPST, and LINC02001. In addition, we performed a gene network interaction analysis using STRINGdb, which revealed a significant relationship between genes predominantly involved in the cell cycle and characterized by upregulated expression in early recurrence. Based on the results, we propose several genes that can be used as potential prognostic markers.

SUBMITTER: Pudova EA

PROVIDER: S-EPMC7859645 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages.

Pudova Elena A EA Krasnov George S GS Kobelyatskaya Anastasiya A AA Savvateeva Maria V MV Fedorova Maria S MS Pavlov Vladislav S VS Nyushko Kirill M KM Kaprin Andrey D AD Alekseev Boris Y BY Trofimov Dmitry Y DY Sukhikh Gennady T GT Snezhkina Anastasiya V AV Kudryavtseva Anna V AV

Frontiers in genetics 20210121

Prostate cancer (PC) is one of the most common cancers among men worldwide, and advanced PCs, such as locally advanced PC (LAPC) and castration-resistant PC (CRPC), present the greatest challenges in clinical management. Current indicators have limited capacity to predict the disease course; therefore, better prognostic markers are greatly needed. In this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets, including RNA-Seq data from the prostate adenocarcino ...[more]

PMID: 33552133

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Project description:BackroundInflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T- and B-cell levels change during carcinogenesis and whether such changes influence disease progression.MethodsThe study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre- and post-diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions-benign biopsy glands (BBG), tumor-adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions-were identified using Time-series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region-specific lymphocyte counts and regional trends.ResultsThe risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG-TAG-MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance.ConclusionsLongitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course.

Dataset Information

Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages.

Publications

Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages.

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