Keywords
Gastrointestinal cancers
Prognosis
Methylation
Tumor immune infiltration
Submitted : 2021-10-31
Accepted : 2021-11-15
Published : 2021-11-30
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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