Research Paper Volume 15, Issue 4 pp 1074—1106
An immune-related prognostic signature associated with immune landscape and therapeutic responses in gastric cancer
- 1 School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
- 2 School of Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- 3 Department of Hematology, Guang’anmen Hospital, Beijing 100053, China
- 4 School of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China
- 5 Department of Gastroenterology, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing 100700, China
Received: August 30, 2022 Accepted: February 13, 2023 Published: February 22, 2023
https://doi.org/10.18632/aging.204534How to Cite
Copyright: © 2023 Sun 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
Immune-related genes (IRGs) have attracted attention in recent years as therapeutic targets in various tumors. However, the role of IRGs in gastric cancer (GC) has not been clearly elucidated. This study presents a comprehensive analysis exploring the clinical, molecular, immune, and drug response features characterizing the IRGs in GC. Data were acquired from the TCGA and GEO databases. The Cox regression analyses were performed to develop a prognostic risk signature. The genetic variants, immune infiltration, and drug responses associated with the risk signature were explored using bioinformatics methods. Lastly, the expression of the IRS was verified by qRT-PCR in cell lines. In this manner, an immune-related signature (IRS) was established based on 8 IRGs. According to the IRS, patients were divided into the low-risk group (LRG) and high-risk group (HRG). Compared with the HRG, the LRG was characterized by a better prognosis, high genomic instability, more CD8+ T cell infiltration, greater sensitivity to chemotherapeutic drugs, and greater likelihood of benefiting from the immunotherapy. Moreover, the expression result showed good consistency between the qRT-PCR and TCGA cohort. Our findings provide insights into the specific clinical and immune features underlying the IRS, which may be important for patient treatment.
Abbreviations
GC: gastric cancer; IRGs: immune-related genes; IRS: immune-related signature; LRG: low-risk group; HRG: high-risk group; TCGA: the cancer genome atlas; GEO: gene expression omnibus; ICI: immune checkpoint inhibitor; TME: the tumor microenvironment; DEGA: differentially expressed gene analysis; DE: differentially expressed; WGCNA: weighted gene co-expression network analysis; GO: gene ontology; KEGG: kyoto genome encyclopedia; GSEA: gene set enrichment analysis; TMB: tumor mutation burden; TIDE: tumor immune dysfunction and exclusion; CGP: cancer genome project; GDSC: genomics of drug sensitivity in cancer; CTRP: cancer therapeutics portal; IC50: half-maximal inhibitory concentrations; HR: hazard ratio; CI: confidence intervals.