新定义的可预测肝癌预后的焦亡相关lncRNA模型  

Identification of a pyroptosis-related lncRNA signature as a novel prognostic biomarker for hepatocellular carcinoma

作　　者：黄威 刘启 陈流华[1] 滕茶香 区喆建 刘韩笑 陈健聪[1] 张昆松[1] Huang Wei;Liu Qi;Chen Liuhua;Teng Chaxiang;Ou Zhejian;Liu Hanxiao;Chen Jiancong;Zhang Kunsong(Center of Hepatic-Pancreatic-Biliary Surgery,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Sun Yat-sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]中山大学附属第一医院肝胆胰外科中心,广州510080 [2]中山大学肿瘤防治中心,广州510060

出　　处：《中华普通外科学文献（电子版）》2023年第5期357-365,共9页Chinese Archives of General Surgery(Electronic Edition)

摘　　要：目的 通过构建细胞焦亡有关的长链非编码核糖核酸(lncRNA)模型,并在独立的肝细胞癌(HCC)患者队列中对其功能进行验证,从而进一步明确HCC中焦亡相关lncRNA的表达及其与预后的相关性。方法 使用癌症基因组图谱(TCGA)队列评估每个焦亡相关lncRNA对生存的预后价值,以构建多基因特征。通过应用最小绝对收缩和选择算子(LASSO)回归法,构建4种lncRNA模型,并将TCGA队列中的所有HCC患者分为低危组或高危组。结果 低危组HCC患者的生存可能性显著高于高危组。风险评分是预测HCC患者预后的独立因素。治疗药物(吉西他滨、多柔比星、丝裂霉素C和索拉非尼)敏感性和免疫细胞(肥大静息细胞、单核细胞、NK静息细胞、CD8+T细胞和M0巨噬细胞)表达量在两组患者之间差异有统计学意义(P<0.05)。基因本体论(GO)和京都基因与基因组大全(KEGG)的分析显示了两组间的差异性富集途径。差异性基因富集分析显示,针对Wnt/β-catenin信号通路有助于制定HCC患者的治疗策略。结论 本研究发现了与焦亡有关的lncRNA新模型,可作为HCC患者的独立预后指标,为制定可靠、精确的癌症治疗方案提供了全新的观点。Objective To clarify the expression of pyroptosis-related lncRNAs in hepatocellular carcinoma(HCC)and their relevance to prognosis by constructing a model of pyroptosis-related lncRNAs and validating their functions in an independent cohort of patients with HCC.Methods A pyroptosis-related multi-lncRNA signature was constructed using a cancer genome atlas(TCGA)cohort to predict the HCC patient prognosis.The least absolute shrinkage and selection operator(LASSO)Cox regression method were used to estalish four lncRNA models and classify all HCC patients into high-risk group or low-risk group.Results The patients in the low-risk group had a better prognosis than the high-risk group,and the risk score was an independent predictor for HCC patients.The sensitivity of drugs such as gemcitabine,doxorubicin,mitomycin C and sorafenib,the expression of immune cells such as mast resting cells,monocytes,NK resting cells,CD8+T cells,and M0 macrophages showed significantly different infiltration degree between the two groups(P<0.05).Enrichment analysis for the differential genes in the two groups of patients was performed.Intriguingly,the result showed that targeting the Wnt/β-catenin signal pathway could help to develop treatment strategies for patients with HCC.Conclusions This study has discovered a signature of pyroptosis-related lncRNA,which can be used as an independent prognostic indicator for HCC patients,providing new insights for reliably and accurately predicting prognosis and developing therapeutic strategies for HCC patients.

关 键 词：肝细胞癌 预后 焦亡 长链非编码核糖核酸 癌症基因组图谱 

分 类 号：R735.7[医药卫生—肿瘤]