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.
Anticancer research. 2023 Jan [Epub]
Manuel Neuberger, Lisa Frey, Katja Nitschke, Frederik Wessels, Niklas Westhoff, Frank Waldbillig, Malin Nientiedt, Friedrich Hartung, Jost VON Hardenberg, Maurice Stephan Michel, Philipp Erben, Philipp Nuhn, Thomas Stefan Worst
Department of Urology and Urological Surgery, Medical Faculty Mannheim of the University of Heidelberg, University Medical Center Mannheim, Mannheim, Germany; ., Department of Urology, University Medical Center, Johannes Gutenberg University, Mainz, Germany., Department of Urology and Urological Surgery, Medical Faculty Mannheim of the University of Heidelberg, University Medical Center Mannheim, Mannheim, Germany.