Beyond PSA: a multi-modal pilot study identifying novel proteomic biomarkers in paraffin-embedded prostate cancer tissue

Abstract

Background Prostate cancer (PCa) is a common and complex disease in men, often progressing from localized to aggressive meta-static stages requiring advanced therapies. Early detection of PCa relies primarily on multiparametric tests, with limitations, like over-diagnosis and lack of specificity. Advances in molecular profiling, particularly proteomics, could enhance patient stratification and personalized therapies. Methods We conducted an analysis using Formalin-Fixed Paraffin-Embedded (FFPE) samples from 23 patients diagnosed with prostatic adenocarcinoma. Proteins were extracted from tissues, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The data were processed to identify proteins and subsequent bioinformatics analysis was performed to uncover significant pathways and potential biomarkers panel. Validation of identified biomarkers was carried out through Western blotting (WB). Results Proteomic profiling identified 1,159 proteins, including 176 significantly elevated in tumor tissues. Enrichment analysis highlighted their involvement in stress response, protein metabolism, and signaling pathways associated with PCa progression. Key pathways included mTORC1 signaling, Myc signaling, and focal adhesion. A biomarker panel consisting of KLK3, GDF15, MIF, and AZGP1 was proposed based on their discriminatory power in distinguishing tumor from normal tissues. WB confirmed the tumor-specific expression of these candidates, particularly GDF15 and KLK3. Conclusions The present study shows for the first time a multi-modal approach that combines a panel of PCa tissue proteins, as a new tool of PCa in patients. The identified biomarker panel offers promise for improving detection and tailoring personalized treatment strategies in PCa management. Further validation in larger cohorts and clinical settings is warranted to establish these findings.