Research Paper Volume 14, Issue 18 pp 7617—7634
Identification and validation of prognostic autophagy-related genes associated with immune microenvironment in human gastric cancer
- 1 Department of Ultrasound, Aero Space Central Hospital, Beijing 100050, China
- 2 Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, China
Received: October 11, 2021 Accepted: September 17, 2022 Published: September 28, 2022
https://doi.org/10.18632/aging.204313How to Cite
Copyright: © 2022 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Autophagy-related genes (ATGs) play critical roles in tumorigenesis and progression in gastric cancer (GC). The present study aimed to identify immune-based prognostic ATGs and verify their functions in tumor immune microenvironment (TIME) in GC. Macrophage infiltration was found to negatively correlate with prognosis in GC patients. After stratifying by infiltration levels of macrophages, we screened The Cancer Genome Atlas and Human Autophagy Database to identify the differentially expressed ATGs (DE-ATGs). Of 1,433 differentially expressed genes between the two groups, seven genes qualified as DE-ATGs. Of these, CXCR4, DLC1, and MAP1LC3C, exhibited strong prognostic prediction ability in Kaplan-Meier survival–log-rank test. High expression of these genes correlated with increased occurrence of advanced grade 3 tumors and poor prognoses. Furthermore, GSEA indicated that they were significantly associated with oncogenic and immune-related pathways. The comprehensive evaluation of TIME via GEPIA, ESTIMATE, CIBERSORT, and TIMER suggested that the three DE-ATGs were closely associated with immune condition, both in terms of immune cells and immune scores. Thus, the outcome of this study may aid in better understanding of the ATGs and their interaction with the immune microenvironment, which would allow the development of novel inhibitors, personalized treatment, and immunotherapy in gastric cancer.
Abbreviations
GC: Gastric cancer; DEG: Differentially-expressed genes; ATGs: Autophagy-related genes; DE-ATGs: Differentially expressed ATGs; TCGA: The Cancer Genome Atlas; OS: Overall survival; TIME: Tumor immune microenvironment; TIICs: Tumor-infiltrating immune cells; ICB: Immune checkpoint blockade.