Proteomic Analysis of Prostate Cancer FFPE Samples Reveals Markers of Disease Progression and Aggressiveness.

Abstract

Simple SummaryProstate cancer (PCa) is the second most frequently diagnosed type of cancer in men. The lack of tools for accurate risk assessment is causing over-treatment of men with indolent PCa but also delayed detection of metastatic disease and thus high mortality. The aim of our study was to identify proteins related to the progression and aggressiveness of PCa that could serve as potential biomarkers for better risk stratification. To this end, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens (n = 86) and compared them based on grade groups and biochemical recurrence status. Based on the valuable data generated by these comparisons, we have selected seven proteins (NMP1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) as common denominators of PCa aggressiveness and persistence that could potentially be used for the development of risk assessment tools. Notably, our observations are largely validated by transcriptomics data and literature.Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy, which might not represent the exact degree of PCa risk. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Comparative analysis of 86 PCa samples among grade groups 1–5 identified 301 significantly altered proteins. Additional analysis based on biochemical recurrence (BCR; BCR+ n = 14, BCR- n = 51) revealed 197 significantly altered proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins (NPM1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness. Notably, all seven proteins were significantly associated with progression in Prostate Cancer Transcriptome Atles (PCTA) and NPM1NPM1, UQCRH, and VCAN were further validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. UQCRH levels were also associated with poorer 5-year survival. Our study provides valuable insights into the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.