Gene Expression Profile of Apatinib Resistance in non-small cell lung Cancer: Integrative Bioinformatics for Therapeutic Insights

Non-Small Cell Lung Cancer (NSCLC) is the predominant form of lung cancer, yet the development of drug resistance poses substantial challenges to its treatment, particularly with the use of Apatinib, a tyrosine kinase inhibitor that offer targeted therapies. This study aims to explore the molecular mechanisms underlying Apatinib resistance in NSCLC through integrative bioinformatics analyses of the publicly available transcriptomics data from the NCBI Gene Expression Omnibus (GEO) database. Specifically, tools GEO2R and Gene Set Enrichment Analysis (GSEA) were applied to identify differentially expressed genes and significant pathways associated with drug resistance by comparing the transcriptomics data across NSCLC lines: the sensitive PC-9 cells, the Gefitinib-resistant PC-9 (PC9GR) cells, and their respective Apatinib-treated counterparts. Key findings included but were not limited to that genes such as ARHGAP28 and TLR4 were significantly upregulated in Gefitinib-resistant cells, while SALL2 and MAP9 were downregulated. The critical pathways in resistance might involve fatty acid metabolism, bile acid metabolism, and Notch signaling. The intersection of differentially expressed genes across various comparisons has highlighted potential biomarkers and therapeutic targets to overcome Apatinib resistance. This study provides comprehensive insights into the gene expression changes and pathway alterations associated with Apatinib resistance in NSCLC. Further investigations, including in vivo studies, are essential to validate these potential targets and improve treatment efficacy.