Research Paper Volume 15, Issue 12 pp 5650—5661
Development and validation of a MUC16 mutation-associated immune prognostic model for lung adenocarcinoma
- 1 Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- 2 Department of Respiratory Medicine, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
- 3 Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
- 4 Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Received: April 3, 2023 Accepted: May 31, 2023 Published: June 20, 2023
https://doi.org/10.18632/aging.204814How to Cite
Copyright: © 2023 Liu 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
Mucin 16 (MUC16) mutation ranks third among all common mutations in lung adenocarcinoma (LUAD), and it has a certain effect on LUAD development and prognostic outcome. This research aimed to analyze the effects of MUC16 mutation on LUAD immunophenotype regulation and determine the prognostic outcome using an immune prognostic model (IPM) built with immune-related genes. The MUC16 mutation status and mRNA expression profiles were analyzed using diverse platforms and among several LUAD patients (n = 691). An IPM was then constructed using differentially expressed immune-related genes (DEIRGs) in MUC16MUT LUAD cases, and the data were compared with those of MUC16WT LUAD cases. The IPM's performance in distinguishing high-risk cases from low-risk ones among 691 LUAD cases was verified. Additionally, a nomogram was built and applied in the clinical setting. Furthermore, a comprehensive IPM-based analysis of how MUC16 mutation affected the tumor immune microenvironment (TIME) of LUAD was performed. MUC16 mutation decreased the immune response in LUAD. As revealed by functional annotation, the DEIRGs in the IPM were most significantly enriched in the humoral immune response function and the immune system disease pathway. Moreover, high-risk cases were associated with increased proportions of immature dendritic cells, neutrophils, and B-cells; enhanced type I interferon T-cell response; and increased expression of PD-1, CTLA-4, TIM-3, and LAG3 when compared with low-risk cases. MUC16 mutation shows potent association with TIME of LUAD. The as-constructed IPM displays high sensitivity to MUC16 mutation status and can be applied to discriminate high-risk LUAD cases from low-risk ones.