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PPP1R14A作为泛癌分析候选物的预后和免疫作用

Prognostic and Immunological Role of PPP1R14A as a Pan-Cancer Analysis Candidate.

作者信息

Wang Zhaotao, Huang Rihong, Wang Haojian, Peng Yuecheng, Fan Yongyang, Feng Zejia, Zeng Zhaorong, Ji Yunxiang, Wang Yezhong, Lu Jiajie

机构信息

Department of Neurosurgery, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China.

出版信息

Front Genet. 2022 May 17;13:842975. doi: 10.3389/fgene.2022.842975. eCollection 2022.

DOI:10.3389/fgene.2022.842975
PMID:35656324
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9152294/
Abstract

Despite emerging evidence revealing the remarkable roles of protein phosphatase 1 regulatory inhibitor subunit 14A (PPP1R14A) in cancer tumorigenesis and progression, no pan-cancer analysis is available. A comprehensive investigation of the potential carcinogenic mechanism of PPP1R14A across 33 tumors using bioinformatic techniques is reported for the first time. PPP1R14A is downregulated in major malignancies, and there is a significant correlation between the PPP1R14A expression and the prognosis of patients. The high expression of PPP1R14A in most cases was associated with poor overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) across patients with various malignant tumors, including adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BLCA), indicated through pan-cancer survival analysis. Receiver operating characteristic (ROC) analysis subsequently exhibited that the molecule has high reference significance in diagnosing a variety of cancers. The frequency of PPP1R14A genetic changes including genetic mutations and copy number alterations (CNAs) in uterine carcinosarcoma reached 16.07%, and these alterations brought misfortune to the survival and prognosis of cancer patients. In addition, methylation within the promoter region of PPP1R14A DNA was enhanced in a majority of cancers. Downregulated phosphorylation levels of phosphorylation sites including S26, T38, and others in most cases took place in several tumors, such as breast cancer and colon cancer. PPP1R14A remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. Our research on the carcinogenic effect of PPP1R14A in different tumors is comprehensively summarized and analyzed and provides a theoretical basis for future therapeutic and immunotherapy strategies.

摘要

尽管越来越多的证据揭示了蛋白磷酸酶1调节抑制剂亚基14A（PPP1R14A）在癌症发生和发展中的显著作用，但尚无泛癌分析。首次报道了使用生物信息学技术对PPP1R14A在33种肿瘤中的潜在致癌机制进行的全面研究。PPP1R14A在主要恶性肿瘤中表达下调，且其表达与患者预后显著相关。通过泛癌生存分析表明，在大多数情况下，PPP1R14A的高表达与包括肾上腺皮质癌（ACC）和膀胱尿路上皮癌（BLCA）在内的各种恶性肿瘤患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）较差相关。随后的受试者工作特征（ROC）分析表明，该分子在诊断多种癌症方面具有较高的参考意义。子宫癌肉瘤中PPP1R14A基因变化（包括基因突变和拷贝数改变（CNAs））的频率达到16.07%，这些改变给癌症患者的生存和预后带来不利影响。此外，PPP1R14A DNA启动子区域的甲基化在大多数癌症中增强。在大多数情况下，包括乳腺癌和结肠癌在内的几种肿瘤中，S26、T38等磷酸化位点的磷酸化水平下调。PPP1R14A与浸润细胞水平和免疫检查点基因显著相关。我们对PPP1R14A在不同肿瘤中的致癌作用进行了全面总结和分析，为未来的治疗和免疫治疗策略提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/307c/9152294/a84a918a9192/fgene-13-842975-g014.jpg
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