Abstract
TRPM2 (transient receptor potential melastatin-2), a Ca2+ permeable, non-selective cation channel, is highly expressed in cancers and regulates tumor cell migration, invasion, and proliferation. However, no study has yet demonstrated the association of TRPM2 with the prognosis of cancer patients or tumor immune infiltration, and the possibility and the clinical basis of TRPM2 as a prognostic marker in cancers are yet unknown. In the current study, we first explored the correlation between the mRNA level of TRPM2 and the prognosis of patients with different cancers across public databases. Subsequently, the Tumor Immune Estimation Resource (TIMER) platform and the TISIDB website were used to assess the correlation between TRPM2 and tumor immune cell infiltration level. We found that 1) the level of TRPM2 was significantly elevated in most tumor tissues relative to normal tissues; 2) TRPM2 upregulation was significantly associated with adverse clinical characteristics and poor survival of kidney renal clear cell carcinoma (KIRC) patients; 3) the level of TRPM2 was positively related to immune cell infiltration. Moreover, TRPM2 was closely correlated to the gene markers of diverse immune cells; 4) a high TRPM2 expression predicted worse prognosis in KIRC based on different enriched immune cell cohorts; and 5) TRPM2 was mainly implemented in the T-cell activation process indicated by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In conclusion, TRPM2 can serve as a marker to predict the prognosis and immune infiltration in KIRC through the regulation of T-cell activation. The current data may provide additional information for further studies surrounding the function of TRPM2 in KIRC.
Highlights
Transient receptor potential (TRP) ion channels are a family of membrane proteins that play diverse physiological and pathological roles
We used the Gene Expression Profiling and Interactive Analysis (GEPIA) database to validate the findings in the Tumor Immune Estimation Resource (TIMER) database and found that, compared to the corresponding normal tissues, the mRNA level of TRPM2 was significantly higher in most human tumors, including bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), acute myeloid leukemia (LAML), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), skin cutaneous melanoma (SKCM), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS) (Figures 1B, C)
The level of TRPM2 was significantly lower in glioblastoma multiforme (GBM) and brain lower-grade glioma (LGG) than that in normal tissue, while no significant differences were detected in sarcoma (SARC), testicular germ cell tumors (TGCT), adrenocortical carcinoma (ACC), diffuse large B-cell lymphoma (DLBC), kidney chromophobe (KICH), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pheochromocytoma and paraganglioma (PCPG), thyroid carcinoma (THCA), and thymoma (THYM) (Figures 1B, C)
Summary
Transient receptor potential (TRP) ion channels are a family of membrane proteins that play diverse physiological and pathological roles. Aberrant regulation of TRP channels results in various diseases, including numerous types of cancer. TRPM2 is a Ca2+-permeable, non-selective cation channel activated by ADP-ribose (ADPR), temperature, oxidative stress, and Ca2+ (Sumoza-Toledo and Penner, 2011b). TRPM2 is ubiquitously distributed in the body, especially highly expressed in many energy-demanding tissues, including the brain, heart, and vasculature. The physiological functions of TRPM2 include insulin secretion in the pancreas, warm sensitivity in neurons (Tan and McNaughton, 2016; ParicioMontesinos et al, 2020), and the induction of dendritic cell maturation and chemotaxis (Sumoza-Toledo et al, 2011a). TRPM2 expressed in immune cells, such as macrophages and polymorphonuclear neutrophils (PMNs), is crucial for regulating the bactericidal activity of phagocytic cells and PMN migration in tissues (Mittal et al, 2017)
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