Identification of expression profiles and transcription factors during EGFR‐TKI acquired resistance in LUAD

Abstract

Abstract Lung cancer is one of the most‐common malignant tumors while lung adenocarcinoma (LUAD) serves as the major subtype of lung cancer. The epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) are an important choice in LUAD targeted therapies. However, EGFR‐TKI acquired resistance always happens, urging for further investigating and overcoming. We acquired the scRNA‐seq data of EGFR‐TKI acquired resistance in LUAD from GSE149383 and PRJNA591860 databases. We identified the typical tendency during EGFR‐TKI acquired resistance progression in LUAD. Furthermore, we investigate the potential expression profiles, upstream transcription factors, and interacting drugs with EGFR‐TKI in LUAD, participating in EGFR‐TKI acquired resistance. According to scRNA‐seq databases, the typical tendency was identified as “decrease early and raise later” during EGFR‐TKI acquired resistance progression in LUAD from Day 0 to Day 11. Seven important pairs of upstream transcription factors and target genes were explored during EGFR‐TKI acquired resistance in LUAD, including TFDP1‐RPA3, TFDP1‐EIF2S1, TFDP1‐COTL1, TFDP1‐CBX1, MYBL2‐STMN1, EZH2‐CYCS, and BRCA1‐STMN1. Several potential interacting drugs with EGFR‐TKI were screened in LUAD, especially TANDUTINIB. We identified the typical tendency of “decrease early and raise later” during EGFR‐TKI acquired resistance progression in LUAD while we recognized transcription factor‐target gene pairs and interacting drugs with EGFR‐TKI during EGFR‐TKI acquired resistance, which could provide a novel insight for clinical treatments.

Keywords

• acquired resistance
• EGFR‐TKI
• LUAD
• single‐cell RNA sequencing