Li Li, Cao Yundi, Fan YingRui, Li Rong
Department of Oncology, The Comprehensive Cancer Centre of Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210000, China.
Department of Medical Oncology, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Open Med (Wars). 2022 Jan 7;17(1):135-150. doi: 10.1515/med-2021-0405. eCollection 2022.
Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis and is the second most fatal cancer, and certain HCC patients also show high heterogeneity. This study developed a prognostic model for predicting clinical outcomes of HCC. RNA and microRNA (miRNA) sequencing data of HCC were obtained from the cancer genome atlas. RNA dysregulation between HCC tumors and adjacent normal liver tissues was examined by DESeq algorithms. Survival analysis was conducted to determine the basic prognostic indicators. We identified competing endogenous RNA (ceRNA) containing 15,364 pairs of mRNA-long noncoding RNA (lncRNA). An imbalanced ceRNA network comprising 8 miRNAs, 434 mRNAs, and 81 lncRNAs was developed using hypergeometric test. Functional analysis showed that these RNAs were closely associated with biosynthesis. Notably, 53 mRNAs showed a significant prognostic correlation. The least absolute shrinkage and selection operator's feature selection detected four characteristic genes (, , , and ), based on which a four-gene independent prognostic signature for HCC was constructed using Cox regression analysis. The four-gene signature could stratify samples in the training, test, and external validation sets ( <0.01). Five-year survival area under ROC curve (AUC) in the training and validation sets was greater than 0.74. The current prognostic gene model exhibited a high stability and accuracy in predicting the overall survival (OS) of HCC patients.
肝细胞癌(HCC)发病率高且预后差,是第二大致命性癌症,并且某些HCC患者还表现出高度异质性。本研究开发了一种用于预测HCC临床结局的预后模型。从癌症基因组图谱获取HCC的RNA和微小RNA(miRNA)测序数据。通过DESeq算法检测HCC肿瘤与相邻正常肝组织之间的RNA失调情况。进行生存分析以确定基本的预后指标。我们鉴定出包含15364对信使核糖核酸(mRNA)-长链非编码核糖核酸(lncRNA)的竞争性内源性RNA(ceRNA)。使用超几何检验构建了一个由8个miRNA、434个mRNA和81个lncRNA组成的失衡ceRNA网络。功能分析表明这些RNA与生物合成密切相关。值得注意的是,53个mRNA显示出显著的预后相关性。最小绝对收缩和选择算子的特征选择检测到四个特征基因(、、和),基于此使用Cox回归分析构建了一个用于HCC的四基因独立预后特征。该四基因特征可在训练集、测试集和外部验证集中对样本进行分层(<0.01)。训练集和验证集中五年生存的受试者工作特征曲线下面积(AUC)大于0.74。当前的预后基因模型在预测HCC患者的总生存期(OS)方面表现出高稳定性和准确性。
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