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

Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer.
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与新陈代谢相关的PPP1R12A相关五基因签名的鉴定和验证,以预测前列腺癌患者的预后。

DOI:
10.3389/fgene.2021.703210
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发表时间:
2021
影响因子:
3.7
通讯作者:
Liang Y
Liang Y
中科院分区:
生物学3区
文献类型:
--
作者:
Zou Z;Liu R;Liang Y;Zhou R;Dai Q;Han Z;Jiang M;Zhuo Y;Zhang Y;Feng Y;Zhu X;Cai S;Lin J;Tang Z;Zhong W;Liang Y

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前列腺癌(PCa)是美国男性人群中最常见的恶性男性肿瘤。我们先前的研究表明,蛋白磷酸酶1调节亚基12 A(PPP 1 R12 A)可能是PCa患者的有效预后因子,促进了进一步的研究。本研究试图构建一个基于PPP 1 R12 A和代谢相关基因的基因标签来预测PCa患者的预后。从TCGA数据库中提取499例肿瘤组织和52例正常组织的mRNA表达谱。我们在这些mRNA中选择了差异表达的PPP 1 R12 A相关基因。串联亲和纯化-质谱法用于鉴定与PPP 1 R12 A直接相互作用的蛋白质。基因集富集分析(GSEA)用于提取代谢相关基因。采用单因素考克斯回归分析和随机生存森林算法确定最佳基因,建立预后风险模型。我们确定了一个与PPP 1 R12 A和PCa代谢相关的五个基因签名(PPP 1 R12 A,PTGS 2,GGCT,AOX 1和NT 5E),其有效地预测了无病生存期(DFS)和生化无复发生存期(BRFS)。此外,通过来自TCGA的两个内部数据集和来自基因表达综合数据库(GEO)的一个外部数据集验证了签名。五基因标签是预测PCa预后的有效潜在因素,将PCa患者分为高风险组和低风险组,这可能为这些患者提供潜在的新治疗策略。
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. The 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. We 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). The 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.
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