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

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

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RIGHTS & PERMISSIONS

2024 The Author(s). Precision Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital.