兰州大学学报（医学版）2025，Vol.51Issue(9)：8-17,10.DOI:10.13885/j.issn.2097-681X.2025.09.002
结直肠癌中缺氧诱导的EGFR抑制剂耐药相关基因的鉴定和机制研究
Identification and mechanism of genes associated with hypoxia-induced resistance to EGFR inhibitors in colorectal cancer
摘要
Abstract
Objective To identify genes,via a bioinformatics analysis,that enhance the therapeutic efficacy of epidermal growth factor receptor(EGFR)inhibitors in colorectal cancer,as well as their potential mechanisms.Methods RNA-Seq data and clinical data for colorectal cancer were obtained from the TCGA database,while hypoxia-associated genes(HRGs)were acquired from the GeneCards database.Kyoto Encyclopedia of Genes and Genomes enrichment analysis was conducted on HRGs to identify potential enrichment pathways.Gene modules associated with colorectal cancer were identified using weighted gene coexpression network analysis(WGCNA),and prognostic models were constructed using univariate Cox regression,LASSO,and multivari-ate Cox regression.Protein-protein interaction network analysis was performed to identify key genes associat-ed with EGFR inhibitor resistance.Subsequently,the Kaplan-Meier Plotter and UALCAN databases were uti-lized to validate the relationship between the model genes,key genes,and colorectal cancer prognosis.The pathway enrichment of these genes was analyzed using the ShinyGO(0.80)database.The clinical value of BCL2L1 was analyzed by GEO database,quantitative polymerase chain reaction and single cell sequencing.Results The HRGs were found to be significantly enriched in the HF-1 signaling pathway,as well as in PI3K/Akt and EGFR inhibitor resistance.WGCNA analysis identified 166 characteristic module genes and estab-lished a prognostic model for colorectal cancer composed of 8 genes,while the protein-protein interaction net-work analysis identified 10 key genes.The prognostic analysis revealed a significant correlation between the expression levels of these genes and the prognosis of colorectal cancer.Furthermore,the expression level of BCL2L1 was significantly higher in the drug-resistant group(P<0.05).Conclusions A model comprising 8 genes was developed to predict the prognosis of patients with colorectal cancer.BCL2L1 plays a crucial role in regulating resistance to EGFR inhibitors in colorectal cancer under hypoxic conditions.关键词
结直肠癌/耐药/缺氧/表皮生长因子受体/单细胞测序分析Key words
colorectal carcinoma/resistance/hypoxia/epidermal growth factor receptor/single cell sequenc-ing analysis分类
医药卫生引用本文复制引用
李桐桐,刘涛,黄翌楚,余春燕,姜雷..结直肠癌中缺氧诱导的EGFR抑制剂耐药相关基因的鉴定和机制研究[J].兰州大学学报（医学版）,2025,51(9):8-17,10.基金项目
国家自然科学基金资助项目(82060527) （82060527）
