Prognostic Significance of GRINA in Colorectal Cancer

Abstract Background: Glutamate Receptor, Ionotropic, N-Methyl D-Aspartate-Associated Protein 1 (GRINA), also named TMBIM3, has been deemed to have oncogenic activities in gastric cancer. However, the role and molecular mechanisms of GRINA in colorectal cancer (CRC) remain largely unknown. We evaluated its prognostic value in CRC by an integrated bioinformatics analysis and experimental verification. Methods: Patients with CRC were derived from TCGA and GTEx databases. We first confirmed the expression profiles of GRINA in human cancers and compared GRINA expression between CRC and normal colorectal tissues by Wilcoxon rank sum test and Wilcoxon signed rank test. χ2 test and logistic regression analysis was used for correlation analysis, and Wilcoxon rank sum test or Kruskal-Wallis rank sum was performed to evaluate the connection between GRINA expression and clinical features. Furthermore, Kaplan-Meier’s analysis and Cox regression analysis were used to assess the correlation between GRINA expression and clinical outcomes. Colony formation and wound-healing assays were performed to observe the impact of GRINA on cell proliferation and motility. GO annotation, PPI network and GSEA were utilized to explore the underlying function of GRINA. Finally, we analyzed the correlation of GRINA in CRC with immune infiltration levels by ssGSEA.Results: We found that GRINA expression was upregulated in diverse human cancer types and especially in CRC. Higher GRINA expression was closely related to unfavorable clinicopathologic features and clinical outcomes. GRINA overexpression promotes CRC proliferation and migration in vitro. Functional enrichment analyses suggested that GRINA is involved in the most significant terms including anion transmembrane transport, cell proliferation related pathways, metabolic pathways and DNA damage and repair related pathways. GRINA expression was most positively correlated with NK CD56dim cells and negatively associated with Th2 cells through analyzing GRINA expression and immune infiltration.Conclusion: GRINA may be a potential prognostic biomarker and therapeutic target in CRC. Moreover, GRINA might accelerate CRC development and EMT by regulating the crosstalk of WNT and MYC signaling which contribute to the unfavorite survival rate and adverse immune infiltration in CRC patients.