Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

Abstract

The histology‐based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label‐free LC‐MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate‐derived proteins including IGKV3D‐20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D‐20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.

Proteomic Landscape of Prostate Cancer: The View Provided by Quantitative Proteomics, Integrative Analyses, and Protein Interactomes

“…Quantitative proteomics studies comparing primary tumors to benign tissue ( Table 1 ) describe a number of DEPs which have been identified between PCa and non-malignant tissue from the same patient [ 59 ], PCa and benign prostatic hyperplasia (BPH) [ 50 , 53 , 56 ], low-risk and high-risk prostate cancer groups [ 46 ], low- and high-grade prostate cancer [ 51 ], different ISUP grades [ 50 ], and even laser-capture microdissection (LCM)-isolated cellular fractions, such as epithelial cells of different Gleason grade [ 48 ] or ERG status [ 60 ]. Although many of these studies find alterations in expression levels of several proteins previously well-known to be aberrantly expressed in prostate cancer, significant heterogeneity exists in the identity of the DEPs identified.…”

MYLK, CNN1, TAGLN and LMOD1 identified as potential prognostic biomarkers for bladder cancer using bioinformatics analysis

“…The last hub gene is LMOD1, also known as Leiomodin-1, could be activated by serum response factor (SRF) or myocardin (MYOCD) and functions in smooth muscle cell differentiation [39]. Previous studies reported that aberrant upregulation of LMOD1 as a poor prognostic marker in a variety of tumors, including colorectal cancer, Leiomyosarcoma and prostate cancer [40][41][42]. The relationship between LMOD1 and the pathogenesis of BCa remain unclear.…”

Prognostic Value of a Stemness Index-Associated Signature in Primary Lower-Grade Glioma

“…Regarding the risk-associated genes, APOBEC3C was discovered as a vital member of the APOBEC family that encodes the APOBEC3C (apolipoprotein B mRNA editing enzyme catalytic subunit 3C, or A3C), clustered in the human chromosome 22 (Jarmuz et al, 2002). Some investigations have shown that the expression of APOBEC3C played a positive role in the invasiveness and prognosis of breast cancer (Zhang et al, 2015;Wang et al, 2019), hepatocellular carcinoma (Yang et al, 2015), and prostate cancer (Kawahara et al, 2019). Taking into account investigations on the role of GNG5 in carcinogenesis, Orchel et al (2012) found that GNG5 may play a vital role in pathogenesis or progression of endometrial cancer.…”