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一种用于改善肝细胞癌预后预测的新型基因组-临床病理列线图。

A novel genomic-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma.

作者信息

Ni Fu-Biao, Lin Zhuo, Fan Xu-Hui, Shi Ke-Qing, Ao Jian-Yang, Wang Xiao-Dong, Chen Rui-Cong

机构信息

The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Wenzhou, Zhejiang 325000, China.

Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.

出版信息

Clin Chim Acta. 2020 May;504:88-97. doi: 10.1016/j.cca.2020.02.001. Epub 2020 Feb 4.

Abstract

There is a lack of precise and clinical accessible model to predict the prognosis of hepatocellular carcinoma (HCC) in clinic practice currently. Here, an inclusive nomogram was developed by integrating genomic markers and clinicopathologic factors for predicting the outcome of patients with HCC. A total of 365 samples of HCC were obtained from the Cancer Genome Atlas (TCGA) database. The LASSO analysis was carried out to identify HCC-related mRNAs, and the multivariate Cox regression analysis was used to construct a genomic-clinicopathologic nomogram. As results, 9 mRNAs were finally identified as prognostic indicators, including RGCC, CDH15, XRN2, RAB3IL1, THEM4, PIF1, MANBA, FKTN and GABARAPL1, and used to establish a 9-mRNA classifier. Additionally, an inclusive nomogram was built up by combining the 9-mRNA classifier (P < 0.001) and clinicopathologic factors including age (P = 0.006) and metastasis (P < 0.001) to predict the mortality of HCC patients. Time-dependent receiver operating characteristic, index of concordance and calibration analyses indicated favorable accuracy of the model. Decision curve analysis suggested that appropriate intervention according to the established nomogram will bring net benefit when threshold probability was above 25%. The genomic-clinicopathologic model could be a reliable tool for predicting the mortality, helping determining the individualized treatment and probably improving HCC survival.

摘要

目前在临床实践中缺乏精确且临床可用的模型来预测肝细胞癌(HCC)的预后。在此,通过整合基因组标志物和临床病理因素开发了一种综合列线图,用于预测HCC患者的预后。从癌症基因组图谱(TCGA)数据库中获取了总共365份HCC样本。进行LASSO分析以鉴定与HCC相关的mRNA,并使用多变量Cox回归分析构建基因组 - 临床病理列线图。结果,最终鉴定出9种mRNA作为预后指标,包括RGCC、CDH15、XRN2、RAB3IL1、THEM4、PIF1、MANBA、FKTN和GABARAPL1,并用于建立一个9 - mRNA分类器。此外,通过结合9 - mRNA分类器(P < 0.001)以及包括年龄(P = 0.006)和转移(P < 0.001)在内的临床病理因素,构建了一个综合列线图,以预测HCC患者的死亡率。时间依赖性受试者工作特征曲线、一致性指数和校准分析表明该模型具有良好的准确性。决策曲线分析表明,当阈值概率高于25%时,根据所建立的列线图进行适当干预将带来净效益。基因组 - 临床病理模型可能是预测死亡率的可靠工具,有助于确定个体化治疗并可能提高HCC患者的生存率。

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