PPP1R18在肾透明细胞癌中的生存预后、肿瘤免疫景观及免疫反应及其潜在的双重机制
Survival Prognosis, Tumor Immune Landscape, and Immune Responses of PPP1R18 in Kidney Renal Clear Cell Carcinoma and Its Potentially Double Mechanisms.
作者信息
Wang Yi, Liu Shouyong, Chen Yinhao, Zhu Bingye, Xing Qianwei
机构信息
Department of Urology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
These authors contributed equally to this work.
出版信息
World J Oncol. 2022 Feb;13(1):27-37. doi: 10.14740/wjon1446. Epub 2022 Feb 28.
BACKGROUND
The aim of this study was to investigate the immunological and prognostic roles of protein phosphatase 1 regulatory subunit 18 (PPP1R18) for overall survival (OS) in kidney renal clear cell carcinoma (KIRC) patients, as well as the prediction of its potential mechanisms.
METHODS
Based on PPP1R18 single gene expression matrices and clinical information from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and GSE6344 datasets, the relationships between PPP1R18 and prognosis/immunity were fully explored. Univariate and multivariate Cox regression analyses were applied to assess its independent prognostic ability and gene set enrichment analysis (GSEA) was implemented to find its related pathways. Besides, we also explored possible mechanisms of PPP1R18 involved in KIRC.
RESULTS
PPP1R18 was highly expressed in KIRC samples than in non-tumor tissues in TCGA, ICGC and GSE6344 datasets, with validations from quantitative real-time polymerase chain reaction (qRT-PCR) in both cell lines and KIRC tissues (all P < 0.05). Univariate and multivariate Cox regression analyses indicated that PPP1R18 was also considered to be with independent prognostic ability in KIRC (both P < 0.01). GSEA results showed that PPP1R18 gene expression was significantly related to Chemokine, JAK STAT, MAPK, and NOTCH pathways. Furthermore, PPP1R18 was also firmly associated with microsatellite instability (MSI), tumor mutational burden (TMB), immune microenvironment, immune cells, immune checkpoints and immune infiltration (all P < 0.05). Analysis of tumor immune dysfunction and exclusion (TIDE) and Imvigor210 datasets suggested that patients with low PPP1R18 expression are more likely to benefit from immunotherapy. Finally, we identified two potential mechanisms of a classical competing endogenous RNA (ceRNA) mechanism and an RNA-binding protein (RBP) involved mechanism of PPP1R18 in KIRC.
CONCLUSIONS
PPP1R18 played oncogenic and immunological roles of OS in KIRC, offering potential antigens for developing KIRC mRNA vaccines.
背景
本研究旨在探讨蛋白磷酸酶1调节亚基18（PPP1R18）在肾透明细胞癌（KIRC）患者总生存期（OS）中的免疫和预后作用，以及对其潜在机制的预测。
方法
基于来自癌症基因组图谱（TCGA）、国际癌症基因组联盟（ICGC）和GSE6344数据集的PPP1R18单基因表达矩阵和临床信息，全面探索PPP1R18与预后/免疫之间的关系。应用单因素和多因素Cox回归分析评估其独立预后能力，并进行基因集富集分析（GSEA）以寻找其相关途径。此外，我们还探讨了PPP1R18参与KIRC的可能机制。
结果
在TCGA、ICGC和GSE6344数据集中，PPP1R18在KIRC样本中的表达高于非肿瘤组织，并通过细胞系和KIRC组织中的定量实时聚合酶链反应（qRT-PCR）进行了验证（所有P<0.05）。单因素和多因素Cox回归分析表明，PPP1R18在KIRC中也被认为具有独立预后能力（均P<0.01）。GSEA结果显示，PPP1R18基因表达与趋化因子、JAK STAT、MAPK和NOTCH途径显著相关。此外，PPP1R18还与微卫星不稳定性（MSI）、肿瘤突变负担（TMB）、免疫微环境、免疫细胞、免疫检查点和免疫浸润密切相关（所有P<0.05）。肿瘤免疫功能障碍和排除分析（TIDE）以及Imvigor210数据集表明，PPP1R18低表达的患者更有可能从免疫治疗中获益。最后，我们确定了PPP1R18在KIRC中的两种潜在机制，即经典的竞争性内源RNA（ceRNA）机制和RNA结合蛋白（RBP）参与机制。
结论
PPP1R18在KIRC中发挥了OS的致癌和免疫作用，为开发KIRC mRNA疫苗提供了潜在抗原。
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