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The discovery of a novel eight-mRNA-lncRNA signature predicting survival of hepatocellular carcinoma patients
Authors:Ye-Min Shi  Yan-Yan Li  Jia-Yun Lin  Lei Zheng  Yi-Ming Zhu  Jian Huang
Affiliation:1. Department of Infections, Yuyao People's Hospital, Medical School of Ningbo University, Ningbo, China;2. Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;3. Department of General Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China;4. Department of Gastroenterology, Yuyao People's Hospital, Medical School of Ningbo University, Ningbo, China
Abstract:Increasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA-lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA-lncRNA signature to improve the ability to predict HCC patients’ survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high-risk group and low-risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648-6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well-performed nomogram integrating the prognostic signature and other clinical information to predict 3- and 5-year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA-lncRNA may be an efficient classification tool to evaluate the prognosis of patients’ with HCC.
Keywords:Cox regression model  hepatocellular carcinoma (HCC)  nomogram  prognostic signature  TCGA
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