Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer.

Zhihao Zou,Yangjia Zhuo,Ren Liu,Rui Zhou,Zhenfeng Tang,Yuanfa Feng,Shanghua Cai,Zhaodong Han,Qishan Dai,Jundong Lin,Weide Zhong,Yuxiang Liang,Xuejin Zhu,Yingke Liang,Minyao Jiang,Yixun Zhang

doi:10.3389/fgene.2021.703210

Abstract

BackgroundProstate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients.MethodsThe mRNA expression profiles of 499 tumor and 52 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. We selected differentially expressed PPP1R12A-related genes among these mRNAs. Tandem affinity purification-mass spectrometry was used to identify the proteins that directly interact with PPP1R12A. Gene set enrichment analysis (GSEA) was used to extract metabolism-related genes. Univariate Cox regression analysis and a random survival forest algorithm were used to confirm optimal genes to build a prognostic risk model.ResultsWe identified a five-gene signature (PPP1R12A, PTGS2, GGCT, AOX1, and NT5E) that was associated with PPP1R12A and metabolism in PCa, which effectively predicted disease-free survival (DFS) and biochemical relapse-free survival (BRFS). Moreover, the signature was validated by two internal datasets from TCGA and one external dataset from the Gene Expression Omnibus (GEO).ConclusionThe five-gene signature is an effective potential factor to predict the prognosis of PCa, classifying PCa patients into high- and low-risk groups, which might provide potential novel treatment strategies for these patients.

Highlights

Prostate cancer (PCa) is the most common male malignancy in the developed world and is predicted to account for ∼26% of new cancer diagnoses among US men and 14.1% worldwide in 2021 (Ferlay et al, 2020; Siegel et al, 2021)
In order to analyze the expression profiles of PPP1R12A in PCa, mRNA expressions levels of PPP1R12A were analyzed by UALCAN, as revealed in 497 PCa samples in The Cancer Genome Atlas (TCGA)
The immunostaining of PPP1R12A protein in benign prostate tissues was markedly stronger than that in PCa tissues, indicating that the protein expression of PPP1R12A was lower in PCa than in normal prostate tissues. These results suggested that PPP1R12A was significantly downregulated in PCa relative to associated normal tissues

Summary

Introduction

Prostate cancer (PCa) is the most common male malignancy in the developed world and is predicted to account for ∼26% of new cancer diagnoses among US men and 14.1% worldwide in 2021 (Ferlay et al, 2020; Siegel et al, 2021). It is demonstrated that the most commonly used clinicopathological factors used to provide important prognostic information for monitoring disease progression in PCa are serum prostatespecific antigen (PSA) level, the Gleason score, the pathological tumor stage, and the surgical margin (Quinn et al, 2001). Prostate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients

Methods

Results

Discussion

Conclusion