Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis

• Published in: Yonsei medical journal Vol. 65; no. 12; pp. 683 - 694
• Main Authors: Kim, Youngtaek, Hwang, Joon Yeon, Kim, Dong Kwon, Lee, Seul, Kang, Seong-san, Baek, Sujeong, Yang, Seung Min, Kim, Mi Hyun, Han, Heekyung, Jeong, Seong Su, Lee, Chai Young, Han, Yu Jin, Sohn, Jie-Ohn, Ye, Sang-Kyu, Pyo, Kyoung-Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.12.2024; 연세대학교의과대학
• Subjects: Anaplastic Lymphoma Kinase - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Cluster Analysis; ErbB Receptors - genetics; Humans; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Mutation; Original; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Single-Cell Analysis; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumor Suppressor Protein p53 - genetics; 의학일반; ScRNA-seq; mutation; TP53 gene; EGFR gene; Non-small cell lung cancer
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2024.0062

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. The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in , , , , , and the wild-type. 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: , , and + mutations (MC1); and , , and 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 , , and chemokines linked to alternative immune pathways. Remarkably, co-occurring and mutations were grouped as MC1. + mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to mutations. In T/NK cells, + mutations showed a higher expression of features related to cell activity and differentiation, whereas mutations showed the opposite. Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.