Bioinformatic Analysis of NR6A1 in Prognosis and Immune Regulation in Gastric Cancer

HOU Jian; LI Jing

doi:10.3969/j.issn.2096-305X.2025.01.009

Abstract：Objective To analyze the role of Nuclear Receptor Subfamily 6 Group A Member 1(NR6A1)in gastric cancer(GC)by bioinformatics,so as to clarify the diagnostic and prognostic value of NR6A1 in GC and its relationship with immune cell infiltration.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the expression differences of NR6A1 in gastric cancer and adjacent tissues.Kaplan-Meier database was used to analyze the relationship between NR6A1 expression and survival prognosis of patients with gastric cancer,and the diagnostic receiver operating characteristic curve(ROC)and nomogram(Nomogram)model were established using the R package.The cBioPortal and MethSurv databases were used to analyze NR6A1 gene mutations and DNA methylation,and the impact on prognosis.Xiantao academic net was used to analyze immune cell infiltration abundance.The STRING database was used to analyze network information about interactions with NR6A1 proteins.The functions of NR6A1-related genes were analyzed by gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG).JASPAR and GRNdb databases were used to predict transcription factors upstream of gene NR6A1.NR6A1 has the function of transcription factor,and its downstream target genes were predicted by GRNdb database,and the functions of related target genes were enriched and analyzed.Results The results of TCGA database showed that NR6A1 was highly expressed in gastric cancer.Kaplan-Meier database suggested that gastric cancer patients with high NR6A1 expression had poor prognosis.ROC curve analysis showed that NR6A1 could be used as a diagnostic marker for gastric cancer tissue(AUC=0.851).Gene mutation analysis showed that the mutation rate of NR6A1 gene was 2.70%,and the prognosis of patients with gene mutation was poor.Methylation analysis showed that among 13 DNA methylation CpG sites,hypomethylation of cg13409170 was associated with poor patient outcomes.Immunoinfiltration analysis showed that the high expression of NR6A1 was negatively correlated with the infiltration of multiple immune cells.GO and KEGG were mainly concentrated in RNA transport and degradation pathways.The upstream transcription factors of NR6A1 gene were predicted to be KLF5 and E2F6 by JASPAR and GRNdb databases.The GRNdb database predicted 7 downstream target genes of transcription factor NR6A1(PLEKHG5,GTF2IRD1,CEL,SPRY2,MSL1,HNF4A-AS1,ADNP-AS1).The functions of target gene enrichment analysis mainly include presynaptic facilitation,Ras protein signal transduction regulation and signal transduction regulation mediated by small GTPase.Conclusion NR6A1 may play a role not only in the development of gastric cancer,but also in the immune regulation of gastric cancer,which indicates that NR6A1 may act as a potential diagnostic and prognostic biomarker in gastric cancer.