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中国癌症防治杂志

中国癌症防治杂志 ›› 2024, Vol. 16 ›› Issue (1): 107-113.doi: 10.3969/j.issn.1674-5671.2024.01.17

• 临床研究 • 上一篇    下一篇

坏死性凋亡相关的长链非编码RNAs生物标志物预测肝细胞癌预后模型的构建

  

  1. 广西医科大学附属肿瘤医院检验科
  • 出版日期:2024-02-25 发布日期:2024-03-08
  • 通讯作者: 欧超 E-mail：ouchaogx@163.com
  • 基金资助:
    广西重点研发计划项目（桂科AB19110007）；广西自然科学基金项目（2017GXNSFAA198015）；广西研究生教育创新计划项目（YCSW2023215）

Construction of a prognostic model for predicting hepatocellular carcinoma by necroptosis⁃ related long non⁃coding RNAs biomarkers

  • Online:2024-02-25 Published:2024-03-08

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摘要： 目的 构建基于坏死性凋亡相关的长链非编码RNAs（necroptosis⁃related long non⁃coding RNAs，NRLs）的肝细胞癌预后模型。方法 从TCGA数据库下载肝细胞癌的转录本数据和临床信息。采用LASSO⁃Cox模型构建预后预测模型，受试者工作特征（receiver operating characteristic，ROC）曲线和校准曲线评估该模型的预测价值，并进行基因集富集分析（gene set enrichment analysis，GSEA）和免疫浸润分析。qRT⁃PCR验证4个NRLs在肝细胞癌细胞Huh7和正常肝细胞MIHA中的差异表达。结果 本研究构建了基于AL117336.2、MKLN1⁃AS、FOXD2⁃AS1、LINC01224等4个NRLs的肝细胞癌风险预后模型。基于训练集构建的风险评分是预后的独立影响因素（HR=1.275， P<0.001）。在训练集中，风险模型预测1、3、5年OS的AUC分别为0.816、0.747、0.752，在测试集中分别为0.713、0.621、0.626，且校准曲线显示模型有较好的一致性。根据中位风险评分将患者划分为高风险组、低风险组，训练集和测试集中高风险组的总存活率均低于低风险组（均P<0.05）。此外，不同风险组中免疫细胞浸润程度和免疫检查点分子的表达差异有统计学意义（均P<0.05）。qRT⁃PCR检测结果显示，4个NRLs在肝细胞癌细胞Huh7中的表达水平均高于正常肝细胞MIHA（均P<0.01）。结论 本研究成功构建了预测肝细胞癌患者预后的NRLs模型，对指导临床治疗具有潜在的价值。

关键词: 肝细胞癌；坏死性凋亡；长链非编码RNAs（lncRNAs）；预后 

Abstract: Objective To construct a prognostic prediction model for hepatocellular carcinoma based on necroptosis⁃related long non⁃coding RNAs (NRLs). Methods Transcript data and clinical information of hepatocellular carcinoma were downloaded from the TCGA database. The LASSO⁃Cox model was used to construct a prognostic prediction model, the predictive value of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and gene set enrichment analysis (GSEA) and immune infiltration analysis were performed. The differential expression of the four NRLs between hepatocellular carcinoma cells Huh7 and normal hepatocytes MIHA was confirmed by qRT⁃PCR. Results A prognostic prediction model was constructed for hepatocellular carcinoma based on four NRLs, including AL117336.2, MKLN1⁃AS, FOXD2⁃AS1, and LINC01224. The risk score constructed based on the training set was an independent factor on prognosis (HR=1.275, P<0.001). The AUCs of 1⁃, 3⁃ and 5⁃year OS predicted by the risk model were 0.816, 0.747 and 0.752, respectively, in the training set, and 0.713, 0.621 and 0.626, respectively, in the testing set. Patients were classified into high and low risk groups based on the median risk score, and the overall survival rate of the high risk group was lower than that of the low risk group in both the training set and the testing set (all P<0.05). In addition, there were significant differences in the degree of immune cell infiltration and the expression of immune checkpoint molecules between the two groups (all P<0.01). qRT⁃PCR results showed that the expression levels of the four NRLs were higher in hepatocellular carcinoma cells Huh7 than in normal hepatocytes MIHA (all P<0.05). Conclusions The NRLs model has been successfully constructed to predict the prognosis of patients with hepatocellular carcinoma, and the constructed model has potential value for guiding clinical treatment.

Key words: Hepatocellular carcinoma, Necroptosis, Long non?coding RNAs (lncRNAs), Prognosis

中图分类号: 

  • R735.7