构建“免疫相关lncRNA基因对”模型预测未发生远处转移的原位肝癌预后及药物敏感性  

Immune-related lncRNA pairs predict the prognosis and drug sensibility of hepatocellular carcinoma without metastases

作　　者：李睿哲 薛军帅 杨龙山 董兆如[1] 洪建国[1] 李涛[1] 王东旭 LI Ruizhe;XUE Junshuai;YANG Longshan;DONG Zhaoru;HONG Jianguo;LI Tao;WANG Dongxu(Department of Hepatobiliary Surgery,Qilu Hospital,Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院肝胆外科,山东济南250012

出　　处：《肝胆胰外科杂志》2022年第7期406-413,共8页Journal of Hepatopancreatobiliary Surgery

摘　　要：目的构建“免疫相关lncRNA基因对”模型预测未发生远处转移的原位肝癌预后并分析不同组别肿瘤免疫微环境特征及药物敏感性。方法从XENA数据库获取肝细胞肝癌样本正常肝脏样本的RNA-seq数据,筛选出未发生远处转移的原位肝癌样本,提取免疫相关lncRNA,构建免疫相关lncRNA基因对的预测模型;随后将免疫相关lncRNA基因对预测模型与患者的预后及临床因素进行相关性分析;同时利用肿瘤免疫细胞浸润数据计算高低风险组免疫微环境特征差异,并评估肝癌相关药物在不同风险组的敏感性。结果筛选出免疫相关lncRNA基因对13个,并结合生存状况建立预测模型,低风险组患者的生存获益显著优于高风险组(P<0.001)。在肿瘤免疫微环境方面,高风险组表现出了更为突出的免疫抑制状态,药物敏感性分析表明索拉非尼、阿昔替尼在基于风险分组的患者中敏感性显著不同。结论免疫相关lncRNA的基因对模型能够较好的预测未发生远处转移的原位肝癌患者预后情况,高风险的患者中免疫抑制状态明显,而不同的风险组对肝癌特定药物治疗敏感性不同。objective The model of“immune-related lncRNA gene pair”was constructed to predict the prognosis of orthotopic liver cancer without distant metastasis,and the characteristics of immune microenviron-ment and drug sensitivity of different groups of tumors were analyzed.Methods RNA-sequencing data of HCC samples and normal liver tissue samples were obtained from XENA database,samples of HCC in situ without distant metastasis were screened out,immune-related lncRNA was extracted,and the prediction model of immune-related lncRNA gene pairs was constructed.Then,the correlation between the prediction model of immune-related lncRNA gene pairs and the prognosis and clinical factors of patients was analyzed.Meanwhile,At the same time,the data of tumor immune cell infiltration were used to calculate the differences of immune microenvironment characteristics between high and low risk groups,and to evaluate the sensitivity of liver cancer-related drugs in different risk groups.Results Thirteen immune-related lncRNA gene pairs were selected from the samples of HCC in situ without distant metastasis,and a prediction model was established based on the survival status.The survival benefit of patients with low risk group was significantly better than that of patients with high risk groups(P<0.001).In terms of tumor immune microenvironment,the high-risk group showed more prominent immunosuppression than the low risk group.Drug sensitivity analysis showed that the sensitivity of Sorafenib and Axitinib was different between patients in high and low risk group.Conclusion The gene pair model of immune-related lncRNA can predict the prognosis of patients with HCC in situ without distant metastasis,and the immunosuppression state is obvious in high-risk patients,while different risk groups have different sensitivities to specific drugs for liver cancer.

关 键 词：肝细胞肝癌 肿瘤预后 癌症基因组图谱数据库(TCGA) 基因型和基因表达量关联数据库(GTEx) 免疫微环境 长链非编码RNA 

分 类 号：R735.7[医药卫生—肿瘤]