Xia Qi, Shu Zheyue, Ye Ting, Zhang Min
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, China.
Front Genet. 2020 Dec 7;11:595699. doi: 10.3389/fgene.2020.595699. eCollection 2020.
As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is the fifth major cause of cancer-associated mortality worldwide. In 90% of cases, HCC develops in the context of liver cirrhosis and chronic hepatitis B virus (HBV) infection is an important etiology for cirrhosis and HCC, accounting for 53% of all HCC cases. To understand the underlying mechanisms of the dynamic chain reactions from normal to HBV infection, from HBV infection to liver cirrhosis, from liver cirrhosis to HCC, we analyzed the blood lncRNA expression profiles from 38 healthy control samples, 45 chronic hepatitis B patients, 46 liver cirrhosis patients, and 46 HCC patients. Advanced machine-learning methods including Monte Carlo feature selection, incremental feature selection (IFS), and support vector machine (SVM) were applied to discover the signature associated with HCC progression and construct the prediction model. One hundred seventy-one key HCC progression-associated lncRNAs were identified and their overall accuracy was 0.823 as evaluated with leave-one-out cross validation (LOOCV). The accuracies of the lncRNA signature for healthy control, chronic hepatitis B, liver cirrhosis, and HCC were 0.895, 0.711, 0.870, and 0.826, respectively. The 171-lncRNA signature is not only useful for early detection and intervention of HCC, but also helpful for understanding the multistage tumorigenic processes of HCC.
作为最常见的恶性肿瘤之一，肝细胞癌（HCC）是全球癌症相关死亡的第五大主要原因。在90%的病例中，HCC在肝硬化的背景下发生，慢性乙型肝炎病毒（HBV）感染是肝硬化和HCC的重要病因，占所有HCC病例的53%。为了了解从正常到HBV感染、从HBV感染到肝硬化、从肝硬化到HCC的动态连锁反应的潜在机制，我们分析了38例健康对照样本、45例慢性乙型肝炎患者、46例肝硬化患者和46例HCC患者的血液lncRNA表达谱。应用包括蒙特卡罗特征选择、增量特征选择（IFS）和支持向量机（SVM）在内的先进机器学习方法来发现与HCC进展相关的特征并构建预测模型。鉴定出171个与HCC进展相关的关键lncRNA，通过留一法交叉验证（LOOCV）评估，其总体准确率为0.823。lncRNA特征对健康对照、慢性乙型肝炎、肝硬化和HCC的准确率分别为0.895、0.711、0.870和0.826。这171个lncRNA特征不仅有助于HCC的早期检测和干预，还有助于理解HCC的多阶段致癌过程。
