• Youngtaek Kim, 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, and Kyoung-Ho Pyo.
• Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
• Yonsei Med. J. 2024 Dec 1; 65 (12): 683694683-694.

PurposeWe 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 MethodsThe 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.ResultsTumor 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.ConclusionOur research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.© Copyright: Yonsei University College of Medicine 2024.

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