Transcriptomic Profiling of Carboplatin- and Paclitaxel-Resistant Lung Adenocarcinoma Cells Reveals CSF3 as a Potential Biomarker for the Carboplatin Plus Paclitaxel Doublet Regimens

This study aimed to generate Car- and Pac-resistant cell lines from the human lung adenocarcinoma H1792 cell line, designated as H1792/Car and H1792/Pac, and perform transcriptome Sequencing to identify potential targets. Common differentially expressed genes (Co-DEGs) in both resistant cell lines were identified, followed by hub gene identification. Online validation was conducted through GEPIA and Kaplan-Meier Plotter platforms, with experimental validation performed using real-time quantitative PCR (RT-qPCR). After six months, the H1792/Car and H1792/Pac cell lines exhibited a 10.7-fold and 5.6-fold increase in resistance to Car and Pac, respectively. Flow cytometry analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and Apoptosis induced by Car or Pac. Transcriptomic Sequencing identified 123 Co-DEGs, including 72 upregulated and 51 downregulated genes, consistently expressed in both H1792/Car and H1792/Pac cell lines. Among these, 13 hub genes were identified, with colony-stimulating factor 3 (CSF3) uniquely associated with post-progression survival (PPS) in adenocarcinoma patients undergoing chemotherapy. Notably, CSF3 expression was significantly elevated in both H1792/Car and H1792/Pac compared to parental cells. These findings underscore the value of drug-resistant models in uncovering critical biomarkers. CSF3 emerges as a promising guiding marker or potential molecular target for optimizing Car- and Pac-based doublet regimens.

biomarkers; carboplatin; chemoresistance; non-small cell lung cancer; paclitaxel; transcriptomic profiling.