CMTM6 as a potential therapy target is associated with immunological tumor microenvironment and can promote migration and invasion in pancreatic adenocarcinoma

Abstract

AbstractCMTM6 has been connected to the development of several malignancies. However, it is still unknown what function CMTM6 serves in pancreatic adenocarcinoma (PAAD). We obtained RNA sequencing information of PAAD from public datasets and predicted statistical significance of CMTM6 survival in accordance with Kaplan–Meier curves. Gene set enrichment assessment (GSEA) was employed to analyze changes in pathways. Then, we systematically investigated the association involving CMTM6 and the immunological traits within the tumor microenvironment (TME) of PAAD, including immune pathways, immunomodulators, immune infiltrating cells, inflammatory activities, and immunotherapy response prediction. To demonstrate the biologically malignant properties of CMTM6 expression, the Cell Counting Kit-8, transwell experiments, colony formation, and wound healing were utilized. Upregulated CMTM6 expression was revealed within PAAD tissues, which was associated with more frequent somatic mutations and worse survival outcomes. Specifically, CMTM6 expression represented stronger immune infiltration, inflammatory activity, and better immunotherapeutic response in TME. Functional studies revealed that CMTM6 promoted the ability to proliferate, migrate, and invade. Additionally, CMTM6 and PD-L1 had a positive relationship, and CMTM6 can co-immunocoprecipitate with PD-L1 protein in pancreatic cell lines. CMTM6 overexpression shapes the inflammatory TME with a strong immune response. These findings support that CMTM6 is an immunotherapeutic target with promising effect to treat PAAD.