PROSTAT KANSERİNDE RİSK STRATİFİKASYONU İÇİN TRANSKRİPTOMİK TEMELLİ BİYOBELİRTEÇLERİN ANALİZİ

Abstract

Turhan, AU., Analysis of Transcriptomic-based Biomarkers for Risk Stratification in Prostate Cancer. Hacettepe University Graduate School of Health Sciences, Tumor Biology and Immunology Program Master’s Thesis, Ankara, 2026. Prostate cancer has a variable clinical course, and current risk assessment is largely based on PSA level, tumor stage, and Gleason score. However, tumor heterogeneity and limited representation by needle biopsies may prevent biopsy-based grading from fully reflecting biological aggressiveness, particularly in biopsy-radical prostatectomy discordance. Although clinicopathological variables and molecular tests contribute to prognostic assessment, their predictive performance, accessibility, and routine applicability remain limited. Therefore, molecular biomarkers that reflect tumor biology and can be evaluated across independent cohorts are needed. In this study, prognostic associations of available genes were investigated in public transcriptomic datasets. TCGA PRAD, GSE220095, and GSE70769 were used for discovery, while DKFZ, GSE116918, and GSE16560 were used for validation. CSRP1 expression was consistently associated with better survival, and multivariable analyses showed that this association was independent of confounding factors. The contribution of CSRP1 to clinical prognostic models was more evident in the Gleason 7 subgroup. After stratification by Decipher risk groups, CSRP1 showed significant prognostic discrimination in low- and intermediate-risk groups. Transcriptomic, mutational, and proteomic analyses showed that low-CSRP1 tumors had more frequent TP53, TTN, and MUC17 mutations, with increased mTORC1-, proliferation-, and lipogenesis-related protein levels. Single-cell RNA-seq analyses showed that CSRP1 expression was mainly observed in the tumor microenvironment, predominantly in smooth muscle cells and fibroblasts, with lower levels in epithelial cells. In vitro, siRNA-mediated CSRP1 knockdown increased cell growth in DU 145 cells. These findings indicate that CSRP1 is a candidate biomarker associated with favorable prognosis in prostate cancer, with consistent performance across cohorts and potential to contribute to clinical risk models.