Abstract
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.
Highlights
As one of the most common malignant tumors and the fifth major cause of cancer deaths worldwide (Jemal et al, 2011), hepatocellular carcinoma (HCC) is typical of highly invasive and metastatic potential
We downloaded the blood long non-coding RNAs (lncRNAs) expression profiles of 38 healthy control samples, chronic hepatitis B patients, liver cirrhosis patients, and 46 HCC sufferers from GSE78160 included in the Gene Expression Omnibus (GEO)
The HCC Progression lncRNAs Identified With Machine Learning Methods
Summary
As one of the most common malignant tumors and the fifth major cause of cancer deaths worldwide (Jemal et al, 2011), hepatocellular carcinoma (HCC) is typical of highly invasive and metastatic potential. Much progress has been made in clinical and experimental studies in HCC, the 5-year survival rate of HCC sufferers is still very low due to its poor prognosis, frequent clinical recurrence, and metastasis (Madkhali et al, 2015). The most important risk factors for liver cancer are hepatitis B virus (HBV), hepatitis C virus (HCV), excessive drinking, and exposure to aflatoxin B1. The geographical variability and heterogeneity of the incidence of HCC is different from the distribution of HBV and HCV infections on a global scale (Liu and Kao, 2007; Petruzziello et al, 2016). HBV accounts for about 80% of virus-related HCC cases, especially in Africa and East Asia, where the incidence of HCC is the highest. In low-incidence HCC areas such as Western
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