2022 World Conference on Lung Cancer (ePosters)-EP16.03-038. Single-cell Analyses Reveal Tumor Microenvironment Differences between EGFR 19del and L858R mutations in Lung Adenocarcinoma

EP16.03-038. Single-cell Analyses Reveal Tumor Microenvironment Differences between EGFR 19del and L858R mutations in Lung Adenocarcinoma

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Lung adenocarcinoma (LUAD) is a common type of lung cancer and is often caused by mutations in the EGFR gene. Two common mutations in EGFR, known as 19del and L858R, have been found to respond differently to treatment with EGFR tyrosine kinase inhibitors (TKIs). In this study, researchers used single-cell RNA sequencing to analyze the tumor microenvironment (TME) differences between LUAD patients with these two EGFR mutations.<br /><br />The researchers obtained single-cell RNA sequencing data from two 19del patients, two L858R patients, and two wild-type patients. They identified different cell types in the TME, including endothelial cells, epithelial cells, fibroblast cells, B/plasma cells, myeloid cells, T cells, and NK cells. While most cell types were similar between 19del and L858R patients, L858R patients had fewer myeloid cells and more fibroblast cells compared to 19del patients.<br /><br />The researchers also found differences in signaling pathways between the two mutation subtypes. The NGF signaling pathway was exclusively detected in L858R patients, while TNF, FASLG, and Sema3A signaling pathways were only detected in 19del patients. These pathways are associated with anti-cancer effects, tumor necrosis, and the inhibition of angiogenesis. These findings provide preliminary insights into why 19del patients may have better clinical outcomes after EGFR TKI treatment.<br /><br />Furthermore, the researchers conducted cell communication analysis and identified 54 signaling pathways shared by both mutation subtypes. However, the NGF signaling pathway was only detected in L858R patients, while TNF, Sema3A, and FASLG signaling pathways were only detected in 19del patients. Additionally, 19del LUAD had stronger communication weights between myeloid cells and T cells compared to L858R LUAD.<br /><br />Overall, this study reveals differences in the TME between EGFR 19del and L858R mutant LUAD patients. Understanding these differences may help improve precision treatments for EGFR mutation patients.

Asset Subtitle

Tao Wang

Meta Tag

Speaker Tao Wang

Topic Tumour Biology and Biomarkers - Molecular Profiling and Targeted Therapies

Keywords

Lung adenocarcinoma

EGFR gene

mutations

19del

L858R

single-cell RNA sequencing

tumor microenvironment

signaling pathways

NGF signaling pathway

precision treatments