Correlations between P2RX1 Expression and Gastrointestinal Cancers Prognosis and Immune Infiltration Based on Bioinformatics Analysis

抗癌研究 Pub Date : 2021-11-30 DOI:10.26689/par.v5i6.2759

Ting Li, Jiankai Feng, Pihong Yan, Hongwei Tan, Lili Wang, Qiang Li, Yun-Peng Yu

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Abstract

This study was conducted to explore the correlations between the expression, methylation, and various clinicopathological factors of purinergic P2X1 receptor (P2RX1) and the prognosis of patients with gastrointestinal tumors. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were used to analyze the expression of P2RX1 in different types of gastrointestinal cancers. Kaplan-Meier analysis and univariate Cox regression analysis were used to analyze the correlations between P2RX1 expression and the prognosis of various gastrointestinal tumors. Correlations between P2RX1 expression and N6 methyladenine (m6A)-related genes as well as immune checkpoint genes were analyzed by R packages (R version: 4.0.3) based on TCGA database. The association between P2RX1 methylation level and the prognosis of patients with gastrointestinal cancers was analyzed using the MethSurv database. In order to explore the biological functions of P2RX1 in hepatocellular carcinoma, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were carried out using R software. In order to evaluate the correlations between P2RX1 and tumor immune infiltration, Spearman correlation test was performed. The correlations between P2RX1 expression and immune score as well as immune checkpoint genes were analyzed based on TCGA and Tumor Immune Estimation Resource (TIMER) databases. The expression of P2RX1 was found to be significantly downregulated in gastrointestinal tumors except in cholangiocarcinoma (P < 0.05). High expression of P2RX1 tended to present better prognosis in hepatocellular carcinoma (P < 0.05). It was noted that cg06475633 of P2RX1 presented a higher methylation level compared with other CpG sites in hepatocellular carcinoma. Overall, six CpGs of P2RX1 were associated with significant prognosis in patients with hepatocellular carcinoma (P < 0.05). Among all the 20 m6A-related genes, Wilms’ tumor 1-associating protein (WTAP) was the most strongly correlated with P2RX1 in hepatocellular carcinoma. Gene enrichment analysis showed that P2RX1 is widely involved in the proliferation, activation, organization, and differentiation of various immune cells. After investigating the TIMER database, P2RX1 was found to be tightly correlated with immune infiltrating cells in gastrointestinal tumors, especially with dendritic cells. Moreover, P2RX1 was found to be strongly positively associated with programmed cell death 1 (PD1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in hepatocellular carcinoma (P < 0.05). In conclusion, the dual role of P2RX1 in cancers and its involvement in the recruitment as well as regulation of tumor infiltrating cells in gastrointestinal cancers may be appreciated through this study.

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基于生物信息学分析的P2RX1表达与胃肠道肿瘤预后和免疫浸润的相关性

本研究旨在探讨嘌呤能P2X1受体（P2RX1）的表达、甲基化和各种临床病理因素与胃肠道肿瘤患者预后之间的相关性。癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库用于分析P2RX1在不同类型的胃肠道癌症中的表达。采用Kaplan-Meier分析和单变量Cox回归分析，分析P2RX1表达与各种胃肠道肿瘤预后的相关性。基于TCGA数据库，通过R软件包（R版本：4.0.3）分析P2RX1表达与N6-甲基腺嘌呤（m6A）相关基因以及免疫检查点基因之间的相关性。使用MethSurv数据库分析P2RX1甲基化水平与胃肠道癌症患者预后之间的关系。为了探讨P2RX1在肝细胞癌中的生物学功能，使用R软件对京都基因与基因组百科全书（KEGG）和基因本体论（GO）进行了富集分析。为了评估P2RX1与肿瘤免疫浸润之间的相关性，进行了Spearman相关性检验。基于TCGA和肿瘤免疫估计资源（TIMER）数据库分析P2RX1表达与免疫评分以及免疫检查点基因之间的相关性。P2RX1在除胆管癌外的胃肠道肿瘤中的表达显著下调（P<0.05）。P2RX1的高表达在肝细胞癌中往往表现出更好的预后（P<0.05），值得注意的是，与肝细胞癌的其他CpG位点相比，P2RX1中的cg06475633表现出更高的甲基化水平。总体而言，P2RX1的6个CpG与肝细胞癌患者的显著预后相关（P<0.05）。在所有20个m6A相关基因中，肝细胞癌中威尔姆斯肿瘤1相关蛋白（WTAP）与P2RX1相关性最强。基因富集分析表明，P2RX1广泛参与各种免疫细胞的增殖、活化、组织和分化。在研究TIMER数据库后，发现P2RX1与胃肠道肿瘤中的免疫浸润细胞，特别是树突状细胞密切相关。此外，P2RX1与肝细胞癌中的程序性细胞死亡1（PD1）、程序性死亡配体1（PD-L1）和细胞毒性T淋巴细胞相关蛋白4（CTLA4）呈正相关（P<0.05），P2RX1在癌症中的双重作用及其参与胃肠道癌症中肿瘤浸润细胞的募集和调节可以通过本研究来认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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抗癌研究

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135