目的 探索口腔鳞状细胞癌(简称口腔鳞癌)顺铂化疗耐药的相关基因及信号通路。方法 建立顺铂诱导的口腔鳞癌细胞耐药模型，将顺铂耐药细胞(HN6-R)与非顺铂耐药细胞(HN6-WT_Control)进行转录组RNA-Seq测序分析，筛选两组中差异表达的基因(DEGs)，利用生物信息学方法分析差异基因及相关信号通路。结果 测序结果显示顺铂耐药细胞与非顺铂耐药细胞有216个基因发生显著变化(log2Fold Change，log2FC＞1;adjusted P value＜0。05)，其中55个基因下调，161个基因上调。对耐药细胞中上调的基因进行了基因富集分析(GSEA)确定了潜在的耐药相关通路，其中包括IL6/JAK2/STAT3信号通路、TNF-α和NF-κB信号通路、低氧通路、干扰素-γ应答和干扰素-α的应答通路等，其中变化最显著的基因为CXCL10、CXCL11、NR4A3和IGFBP3等。结论 IL6/JAK2/STAT3等信号通路在口腔鳞癌顺铂耐药细胞株中显著上调，可能成为预测口腔鳞癌化疗疗效的标志物及潜在的治疗靶点。
Investigating cisplatin drug resistance mechanisms in oral squamous cells carcinoma through RNA-Seq technology:a preliminary study
Objective Investigating the genes and signaling pathways related to cisplatin chemoresistance in oral squamous cell carcinoma(OSCC).Methods We established an in vitro model of cisplatin-induced resistance in an OSCC cell line.Using RNA sequencing,we compared the transcriptomic difference of cisplatin-resistant(HN6-R)and sensitive(HN6-WT_Control)cell lines.Differential expression analysis was conducted to identify key genes and pathways involved in chemoresistance.Gene set enrichment analysis(GSEA)was utilized to fur-ther elucidate the biological significance of these changes.Results Transcriptomic analysis revealed 216 differen-tially expressed genes(DEGs)in HN6-R cells,including 55 downregulated and 161 upregulated genes,relative to HN6-WT_Control cells(log2Fold Change＞1;adjusted P value＜0.05).GSEA analysis identified several critical pathways associated with chemoresistance,notably the IL6/JAK2/STAT3,TNF-α and NF-κB,and vari-ous immune response pathways.Prominent among the altered genes were CXCL10,CXCL11,NR4A3,and IG-FBP3.Conclusion Our findings highlight the upregulation of IL6/JAK2/STAT3 and other immune-related path-ways in cisplatin-resistant OSCC cells,suggesting their potential as biomarkers for chemotherapy response and as therapeutic targets.This study provides new insights into the molecular mechanisms of cisplatin resistance in OS-CC,offering a foundation for future research and therapeutic development.
国家科技期刊平台
NSTL
万方数据
维普
