Identification of immune-related gene signature for non-small cell lung cancer patients with immune checkpoint inhibitors

Li Wang; Chaonan Han; Chenlei Cai; Jing Wu; Jianing Chen; Chunxia Su

doi:10.1016/j.heliyon.2024.e26974

Identification of immune-related gene signature for non-small cell lung cancer patients with immune checkpoint inhibitors

Heliyon. 2024 Feb 27;10(5):e26974. doi: 10.1016/j.heliyon.2024.e26974. eCollection 2024 Mar 15.

Authors

Li Wang¹, Chaonan Han¹, Chenlei Cai¹, Jing Wu¹, Jianing Chen¹, Chunxia Su^{1

2}

Affiliations

¹ Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China.
² Department of Clinical Research Center, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China.

Abstract

Background: The utilization of immune checkpoint inhibitors (ICIs) has become the established protocol for treating advanced non-small cell lung cancer (NSCLC). This work aimed to identify the immune-related gene signature that can predict the prognosis of NSCLC patients receiving ICI treatment.

Methods: The ImmPort database was queried to obtain a list of immune-related genes (IRGs). Differentially expressed IRGs in NSCLC patients were identified using the TCGA database. RNA-seq data and clinical information from NSCLC patients receiving immunotherapy were obtained from the GEO database (GSE93157 and ////). A gene signature was generated through multivariate Cox and LASSO regression analyses. The prognostic value and function of this gene signature were thoroughly investigated using comprehensive bioinformatics analyses.

Results: A total of 6 prognostic-related genes were identified from 617 differentially expressed genes, and two prognostic-related differentially expressed genes (CAMP and IL17A) were determined to construct gene signature. Our gene signature demonstrated superior performance compared to other clinicopathological parameters in predicting the prognosis of NSCLC patients receiving immunotherapy, with an area under the ROC curve (AUC) of 0.812. Furthermore, immune infiltration analysis indicated that the high-risk group was enriched with resting CD4 T cell memory, while the low-risk group showed a "hot" tumor microenvironment that promotes anti-tumor immunity in NSCLC patients.

Conclusion: Gene signatures based on immune-related genes exhibited excellent indicator performance of prognosis and immune infiltration, which has the potential to be an effective biomarker for NSCLC with ICI treatment.

Keywords: Gene signature; Immune checkpoint inhibitors; Immune infiltration; Immune-related gene; NSCLC.