Raungrut Pritsana, Tanyapattrapong Suchanan, Masjon Thipphanet, Maungchanburi Saowanee, Thongsuksai Paramee
Division of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkhla University, Hat Yai 90110, Songkhla, Thailand.
Department of Pathology, Faculty of Medicine, Prince of Songkhla University, Hat Yai 90110, Songkhla, Thailand.
Curr Issues Mol Biol. 2024 Dec 11;46(12):13951-13969. doi: 10.3390/cimb46120834.
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 () uniquely associated with post-progression survival (PPS) in adenocarcinoma patients undergoing chemotherapy. Notably, 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. emerges as a promising guiding marker or potential molecular target for optimizing Car- and Pac-based doublet regimens.
本研究旨在从人肺腺癌H1792细胞系中产生对卡铂（Car）和紫杉醇（Pac）耐药的细胞系，命名为H1792/Car和H1792/Pac，并进行转录组测序以鉴定潜在靶点。鉴定了两种耐药细胞系中的共同差异表达基因（Co-DEGs），随后进行枢纽基因鉴定。通过GEPIA和Kaplan-Meier Plotter平台进行在线验证，并使用实时定量PCR（RT-qPCR）进行实验验证。六个月后，H1792/Car和H1792/Pac细胞系对卡铂和紫杉醇的耐药性分别增加了10.7倍和5.6倍。流式细胞术分析表明，两种耐药细胞系均对卡铂或紫杉醇诱导的细胞周期停滞和凋亡具有抗性。转录组测序鉴定出123个Co-DEGs，包括72个上调基因和51个下调基因，在H1792/Car和H1792/Pac细胞系中均持续表达。其中，鉴定出13个枢纽基因，集落刺激因子3（）与接受化疗的腺癌患者的进展后生存（PPS）唯一相关。值得注意的是，与亲本细胞相比，在H1792/Car和H1792/Pac中 的表达均显著升高。这些发现强调了耐药模型在揭示关键生物标志物方面的价值。 作为优化基于卡铂和紫杉醇的双联方案的有前景的指导标志物或潜在分子靶点出现。
