Abstract
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 (SAPCD2, DKC1, CHRNA5, and UROD), 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 (p <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.
Highlights
Hepatocellular carcinoma (HCC), which is a malignant tumor originating from hepatocytes, accounts for more than 80% of all types of liver cancer
One long noncoding RNA (lncRNA) tended to form a competing endogenous RNA (ceRNA) network with multiple genes, and the degree distribution showed a power-law distribution
This was consistent with the characteristics of biological networks (Figure 2b), indicating that ceRNA was potentially associated with liver-regulated networks in HCC
Summary
Hepatocellular carcinoma (HCC), which is a malignant tumor originating from hepatocytes, accounts for more than 80% of all types of liver cancer. HCC is ranked as the third most common malignancy globally and is highly prevalent in Asia including in China [1]. 782,000 new HCC cases and 746,000 death cases were reported in 2012 all over the world [2]. HCC is likely to develop postoperative metastasis and recurrence, which will greatly affect the treatment outcome. The underlying molecular mechanism involved in rapid progression and high mortality of HCC is poorly understood, which points to the need to searching new molecular targets and developing new therapeutic strategies to facilitate early diagnosis and treatment of HCC and improve the overall survival of HCC patients
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