Identification of CSRP1 as novel biomarker for hormone-sensitive prostate cancer by the combination of clinical and functional research.

Abstract

Prostate cancer (PCa) ranks as the second most common malignancy and the fifth leading cause of cancer-related deaths among men. A critical challenge lies in accurately identifying those patients at high risk for transitioning rapidly from hormone-sensitive PCa (HSPC) to lethal castration-resistant PCa (CRPC). In our study, we employed a multiomics approach involving bioinformatics analysis on datasets GSE2443 and GSE35988, along with proteomics studies, to discover that cysteine- and glycine-rich protein 1 (CSRP1) expression significantly impacts the progression of HSPC. This hypothesis was substantiated through experiments using PC3 and LNCaP prostate cancer cells, where we conducted scratch assays and apoptosis assays, all of which confirmed CSRP1's role in suppressing tumor growth. Furthermore, we elucidated the inhibitory effect of CSRP1 on tumors by performing xenograft experiments on castrated mice models. To solidify these findings in a clinical context, we constructed a nomogram model integrating CSRP1's immunohistochemistry data and clinical parameters from an actual patient cohort with HSPC. This model revealed that low CSRP1 expression indeed promotes the advancement towards CRPC. In conclusion, the level of CSRP1 expression can serve as a valuable biomarker for clinicians to predict disease progression in their patients. It has the potential to guide personalized clinical management and decision-making strategies, thereby contributing to more effective and targeted treatment approaches for HSPC patients.