ATG9B Is a Poor Prognostic Marker Associated With Immune Evasion in Colon Adenocarcinoma

Abstract

Background/aim: Autophagy-related genes (ATGs) are involved in autophagy activation, which has a pleiotropic role in cancer development. However, the potential value of ATG expression levels in colon adenocarcinoma (COAD) is unclear. This study aimed to examine the modulation of ATG expression levels and their association with clinical and molecular aspects of COAD.

Materials and methods: We used the clinical and molecular phenotypes and RNA sequencing datasets of the cancer genome atlas (TCGA)-COAD project using TCGAbiolinks and cBioPortal. Comparisons of ATG expression levels between tumor and normal tissues were performed using DESeq2 within R. Gene expression and immune cell infiltration levels were analyzed by TIMER.

Results: ATG9B had the highest expression levels among ATGs in COAD tissues compared to normal tissues and was related to advanced stage and poor prognosis in COAD. In addition, ATG9B expression was positively associated with the consensus molecular subtype 4 and chromosomal instability but negatively correlated with tumor mutation burden. Furthermore, high ATG9B expression levels were associated with low immune cell infiltration and decreased expression of natural killer cell activation genes.

Conclusion: ATG9B is a poor prognostic biomarker driving immune evasion of COAD through negative correlation with immune cell infiltration.

Keywords: Autophagy; chromosomal instability; colonic neoplasms; immune evasion; tumor microenvironment.