SLIT/ROBO Pathway and Prostate Cancer: Gene and Protein Expression and Their Prognostic Values

Abstract

Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer-related mortality among men. Gene expression analysis has been crucial in understanding tumor biology and providing disease progression markers. Cell surface glycoproteins and those in the extracellular matrix play significant roles in the PCa microenvironment by promoting migration, invasion, and metastasis. The molecular and histopathological heterogeneity of prostate tumors necessitates a new marker discovery to better stratify patients at risk for poor prognosis. In this study, our objectives were to investigate and characterize the localization and expression of SLIT/ROBO in PCa samples from transgenic mice and human tumor samples, aiming to identify novel prognostic markers and potential therapeutic targets. We conducted histopathological, immunohistochemical, and bioinformatics analyses on prostate tumors from two <i>knockout</i> mice models (<i>Pb-Cre4/Pten^f/f</i> and <i>Pb-Cre4/Trp53^f/f;Rb1^f/f</i>) and human prostate tumors. Transcriptomic analyses revealed special changes in the expression of genes related to the SLIT/ROBO neural signaling pathway. We further characterized the gene and protein expression of the SLIT/ROBO pathway in knockout animal samples, and protein expression in the PCa samples of patients with different Gleason scores. Public datasets with clinical data from patients (The Human Protein Atlas, cBioPortal, SurvExpress and CamcAPP) were used to validate the gene and protein expression of SLIT1, SLIT2, ROBO1, and ROBO4, correlating these alterations with the prognosis of subgroups of patients. Our findings highlight potential biomarkers of the SLIT/ROBO pathway with prognostic and predictive value, as well as promising therapeutic targets for PCa.