Pan-cancer analysis of ARMCX genes identifies ARMCX1 as a novel suppressor gene for pancreatic carcinoma

Abstract

Abstract Background: Pancreatic carcinoma (PAAD) is one of the malignant tumors with high lethality and low survival rate. Armadillo (ARMCX) family members play vital roles in tumorigenesis, but the tumorigenesis was not unclear. Our study aims to explore the novel biomarker of early diagnosis, treatment, and prognosis for PAAD. Methods: Firstly, UCSC Xena was used to download the data of pan-cancer. Then, we perform the pan-cancer analysis of ARMCX genes from expression, survival, immune subtype, tumor microenvironment, and stemness. Secondly, we focus on the roles of ARMCX genes in PAAD from the immune subtype, tumor microenvironment, and stemness. Lastly, we used GEIPA to select a key gene, and ARMCX1 was selected as our object. We analyzed the roles of ARMCX1 in PAAD from the differential expression, survival, independent prognosis, clinical features, mechanism, DNA methylation levels, immune cell infiltration, and immunoinhabitors. Results: Based on the pan-cancer analysis, we deem that the differential expression of ARMCX genes exists in multiple tumors, which is closely associated with OS of multiple tumor patients. Plus, we also found that the expression is negatively related to immune subtypes, estimate score, immune score, stromal score, and stemness score. Based on the PAAD analysis, we found that the expression of ARMCX1 and ARMCX4 was significantly different in the immune subtype and a significant difference exists in RNAss, DNAss, stromal score, immune score, and estimate score. Based on the study of ARMCX1 in PAAD, We deemed that ARMCX1 is a lower expression in PAAD than in normal pancreas tissue, and the low expression is closely associated with poor OS of PAAD patients. ARMCX1 is an independent prognosis factor for PAAD patients. In addition, the downregulation of ARMCX1 is also closely associated with hypermethylation of the ARMCX1 promoter. We also found that the expression of ARMCX1 is related to some immune cells and immunoinhibitors. Conclusion: Therefore, we concluded that hypermethylation of the ARMCX1 promoter leads to the downregulation of ARMCX1 expression and inhabits the PAAD progression through influencing the immune cell by some potential mechanism.