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

Jianxin Li¹, Ting Han¹, Jieyi Yang¹, Xin Wang¹, Yinchun Wang¹, Rui Yang¹, Qingqiang Yang¹

¹Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, P.R. China

* Equal contribution

Received: December 26, 2023Accepted: April 15, 2024Published: June 25, 2024

https://doi.org/10.18632/aging.205968

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.