基于基因数据集和分子对接技术的非小细胞肺癌 EGFR-TKIs耐药/敏感相关核心基因筛选.

Objective To identify the epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitors (TKIs) - related genes in non-small-cell lung cancer (NSCLC) based on transcriptome data and molecular docking, and to observe their effect on the sensitivity to EGFR-Tkis drugs (Afatinib, AZD-9291, Erlotinib, Gefitinib). Methods The differen‐ tially expressed genes of EGFR-TKIs resistant cell lines and sensitive cell lines in four gene datasets of GEO database were collected to obtain common differentially expressed genes. Pearson correlation analysis was used to analyze the correlation between common differentially expressed genes and the IC50 of EGFR-TKIs based on CellMiner data. Gene-drug pairs were initially screened, and molecular docking method was used to screen and verify gene-drug pairs. Results The EGFRTKIs sensitive cell lines in the four gene datasets shared 42 up-regulated genes and 14 down-regulated genes. A total of 16 gene-drug pairs meeting the criteria were initially screened out, including 7 EGFR-TKIs-related genes, namely LITAF, MUC16, ERBB2, C1orf116, MBNL3, SYK and TSPAN4. The expression levels of LITAF, MUC16, ERBB2, C1orf116, MBNL3 and SYK were negatively correlated with the IC50 of EGFR-TKIs (all P<0. 05), and the expression of TSPAN4 was positively correlated with the IC50 of EGFR-TKIs (P<0. 05). Molecular docking results showed that only 5 pairs of key com‐ ponents of EGFR-TKIs had good binding activity with corresponding targets, including ErBB2-Afatinib, Erbb2-AZD9291, Erbb2-Erlotinib, MUC16-Afatinib, MUC16-Erlotinib and MUC16-Gefitinib, respectively. Conclusions The core genes related to EGFR-TKIs sensitivity/resistance in NSCLC are MUC16 and ERBB2. Overexpression of MUC16 can improve their sensitivity to Afatinib and Erlotinib, and overexpression of ERBB2 can improve their sensitivity to Afatinib, Erlotinib and AZD-9291. [ABSTRACT FROM AUTHOR]