Integrin Expression in Localized Prostate Cancer: A TCGA and MSKCC Cohort-based Exploratory In Silico Analysis

• Published in: Anticancer research 2023-01, Vol.43 (1), p.417-428
• Main Authors: Neuberger, Manuel, Frey, Lisa, Nitschke, Katja, Wessels, Frederik, Westhoff, Niklas, Waldbillig, Frank, Nientiedt, Malin, Hartung, Friedrich, VON Hardenberg, Jost, Michel, Maurice Stephan, Erben, Philipp, Nuhn, Philipp, Worst, Thomas Stefan
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Angiogenesis; Antigens; Biomarkers; Cohort Studies; Genomes; Humans; Integrins; Male; Metastases; Neoplasm Staging; Phenotypes; Prognosis; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms - pathology; Regression analysis; Retrospective Studies; Statistical analysis; Statistical tests; Tumors
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.16177

Diagnostic and prognostic biomarkers in localized prostate cancer (PC) are insufficient. Treatment stratification relies on prostate-specific antigen, clinical tumor staging and International Society of Urological Pathology (ISUP) grading, whereas molecular profiling remains unused. Integrins (ITG) have an important function in bidirectional signaling and are associated with progression, proliferation, perineural invasion, angiogenesis, metastasis, neuroendocrine differentiation, and a more aggressive disease phenotype in PC. However, ITG subunit expression in localized PC and their utility as prognostic biomarkers has not yet been analyzed. This study aimed to fill this gap and provide a comprehensive overview of ITG expression as well as ITG utility as biomarkers. The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering Cancer Center (MSKCC) prostate adenocarcinoma cohorts were analyzed regarding ITG expression in correlation to ISUP, N- and American Joint Committee on Cancer (AJCC) stage and were correlated with disease-free survival (DFS). Statistical tests used included the Mann-Whitney U-test, logrank test and uni- and multivariable cox regression analyses. After grouping for ISUP (1 and 2 vs. 3-5), N0 vs. N1 and AJCC stage (≤2 vs. ≥3), multiple ITGs showed significant expression differences. The most consistent results were observed for ITGα4, ITGαX, ITGα11, ITGβ2 and ITGα2. In multivariable cox regression, ITGα2, ITGα10, ITGαD, ITGαB2 (TCGA), ITGα11 and ITGβ4 (MSKCC) were independent predictors of DFS. The utility of ITGs as PC biomarkers was herein shown.