Research Paper Volume 16, Issue 14 pp 11185—11207
Identification of immunotherapy-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognostic signature in gastric carcinoma
- 1 Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, P.R. China
Received: December 26, 2023 Accepted: April 15, 2024 Published: June 25, 2024
https://doi.org/10.18632/aging.205968How to Cite
Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types, the present study aimed to explore the immunotherapy-related genes (IRGs) and develop a prognostic risk signature in gastric carcinoma (GC) based on these genes.
Methods: IRGs were identified by comparing immunotherapy responders and non-responders in GC. Then, GC patients were divided into distinct subtypes by unsupervised clustering method based on IRGs, and the differences in immune characteristics and prognostic stratification between these subtypes were analyzed. An immunotherapy-related risk score (IRRS) signature was developed and validated for risk classification and prognosis prediction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Besides, the predictive ability of the IRRS in immunotherapy response was also determined.
Results: A total of 63 IRGs were identified, and 371 GC patients were stratified into two molecular subgroups with significantly different prognosis and immune characteristics. Then, an IRRS signature comprised of three IRGs (CENP8, NRP1, and SERPINE1) was constructed to predict the prognosis of GC patients in TCGA cohort. Importantly, external validation in multiple GEO cohorts further confirmed the universal applicability of the IRRS in distinct populations. Furthermore, we found that the IRRS was significantly correlated with patient’s responsiveness to immunotherapy, GC patients with low IRRS are more likely to benefit from existing immunotherapy.
Conclusions: The risk score could serve as a robust prognostic biomarker, provide therapeutic benefits for immunotherapy and may be helpful for clinical decision making in GC patients.
Abbreviations
GC: gastric carcinoma; IRG: immunotherapy-related gene; IRRS: immunotherapy-related risk score; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; OS: overall survival; TNM: tumor, lymph node, metastasis; TME: tumor microenvironment; ICI: checkpoint inhibitor; PD-1: programmed death 1; PD-L1: programmed death ligand 1; CTLA–4: cytotoxic T lymphocyte-associated antigen-4; FDA: Food and Drug Administration; NCCN: National Comprehensive Cancer Network; CSCO: Chinese Society of Clinical Oncology; TIDE: Tumor Immune Dysfunction and Exclusion; CNV: copy number variation; IPS: immunophenoscore; STAD: Stomach Adenocarcinoma; TCIA: The Cancer Immunome Atlas; KEGG: Kyoto Encyclopedia of Genes and Genomes; DAVID: Database for Annotation, Visualization and Integrated Discovery; TMB: tumor mutation burden; ICB: immune checkpoint biomarker; DEG: differentially expressed gene; GO: gene ontology; ROC: receiver operating characteristic; PR: partial response; CR: complete response; PD: progressive disease; SD: stable disease; PFS: progression free survival; MSI-H: microsatellite instability-high; AUC: area under ROC; MSS: microsatellite stability; RFS: relapse-free survival; IFNγ: interferon-γ; TNF: tumor necrosis factor; ADCC: antibody-dependent cell-mediated cytotoxicity; TIL: tumor-infiltrating lymphocytes.