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

Abstract

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.

Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence

“…These findings support the idea that as PCas become androgen-insensitive, progression may be partly driven by ER-mediated pathways either in the cancer itself or through ER-mediated signaling in the stroma creating a permissive microenvironment favoring tumor progression Interrogation of the gene panel showed a prominent role of the EMT in relation to BCR. Kaplan Meier analysis indicated that high expression of VCAN (Log-Rank test P =0.04) was associated with a significantly lower BCRFS, consistent with the recognition of VCAN-mediated progression ( 80 ). VCAN expression is regulated by SNAIL , which is proposed to bind to the gene’s promoter region ( 88 ).…”

Identification of prognostic signature of cancer-associated fibroblasts associated with castration resistance prostate cancer based on Weighted Gene Co-expression Network Analysis

“…Currently, some CAF prognostic markers had been con rmed to be associated with PCa progression. A recent proteomic study on PCa para n-embedded (FFPE) tissue samples showed that protein VCAN is associated with biochemical recurrence of PCa, could be a prognostic marker (Lygirou et al 2022). another study con rmed that FAP has potential as a diagnostic and therapeutic target, and PCa tissue could be better visualized in positron emission tomography/computed tomography (PET/CT) using a developer targeting FAP (Boinapally et al 2022).…”

Biomarkers for the Detection and Risk Stratification of Aggressive Prostate Cancer

“…This classifier comprised a panel of five proteins (i.e., FOLH1, KLK3, TGFB1, SPARC, and CAMKK2) that are capable of stratifying PCa patients according to the risk of aggressiveness [ 108 ]. In a recent study, seven differentially expressed proteins (i.e., HSPA9 and HSPE1, NPM1, VCAN, SERBP1, MRPL3, and UQCRH) were successfully used as indicators of PCa progression and aggressiveness [ 109 , 110 ]. Using gene enrichment and immunohistochemical analyses, POSTN, CALR, and CTSD were found to be associated with PCa progression and short patient survival [ 111 ].…”