Clinical and Molecular Characteristics, Transcriptome, and Drug Efficacy of ERBB2 Tyrosine Kinase and Non-Tyrosine Kinase Mutations in Non-Small Cell Lung Cancer

ERBB2 mutations in the tyrosine kinase domain (TKD) have been widely reported in non-small cell lung cancer (NSCLC). More and more non-tyrosine kinase domain (non-TKD) mutations of ERBB2 have been detected. However, the clinical effects of non-TKD mutations are still unknown. Therefore, this study aims to study the molecular and clinical characteristics, transcriptome differences, and sensitive drugs of TKD and non-TKD mutations in NSCLC. Gene mutation, RNA sequencing, and clinical information of NSCLC with ERBB2 mutations were downloaded. Bioinformatics methods, such as gene mutation analysis, differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI), hub gene identification, and drug sensitivity analysis, were adopted. Finally, four patients were included to reflect the treatment response. The somatic mutation rate of ERBB2 was 3.2%. TKD and non-TKD mutations mainly occurred in lung adenocarcinoma. Non-TKD mutations have a better prognosis. Up-regulated DEGs are primarily involved in immune and inflammatory pathways. We then proved that BTK, LYN, and PIK3CA mutations have a better prognosis than wild type in patients of NSCLC. The drug sensitivity study found that the TKD group was more sensitive to 5 drugs, and the non-TKD was 28.TKD and non-TKD mutations identify two independent subsets of ERBB2 mutations in NSCLC. Non-TKD mutations have a better prognosis and can also be used as targets for ERBB2. Our study can provide a foundation for further clinical research, highlighting the importance of individualized treatment for patients with different mutation domains.