Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
- Author:
Youngtaek KIM
1
;
Joon Yeon HWANG
;
Kwangmin NA
;
Dong Kwon KIM
;
Seul LEE
;
Seong-san KANG
;
Sujeong BAEK
;
Seung Min YANG
;
Mi Hyun KIM
;
Heekyung HAN
;
Seong Su JEONG
;
Chai Young LEE
;
Yu Jin HAN
;
Jie-Ohn SOHN
;
Sang-Kyu YE
;
Kyoung-Ho PYO
Author Information
- Publication Type:Original Article
- From:Yonsei Medical Journal 2024;65(12):683-694
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion:Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
