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BACKGROUND: Early recurrence is the main obstacle for long-term survival of hepatocellular carcinoma (HCC) patients after curative resection. OBJECTIVE: We aimed to develop a long non-coding RNA (lncRNA) based signature to predict early recurrence. METHODS: Using bioinformatics analysis and quantitative reverse transcription PCR (RT-qPCR), we screened for lncRNA candidates that were abnormally expressed in HCC. The expression levels of candidate lncRNAs were analyzed in HCC tissues from 160 patients who underwent curative resection, and a risk model for the prediction of recurrence within 1 year (early recurrence) of HCC patients was constructed with linear support vector machine (SVM). RESULTS: An lncRNA-based classifier (Clnc), which contained nine differentially expressed lncRNAs including AF339810, AK026286, BC020899, HEIH, HULC, MALAT1, PVT1, uc003fpg, and ZFAS1 was constructed. In the test set, this classifier reliably predicted early recurrence (AUC, 0.675; sensitivity, 72.0%; specificity, 63.1%) with an odds ratio of 4.390 (95% CI, 2.120–9.090). Clnc showed higher accuracy than traditional clinical features, including tumor size, portal vein tumor thrombus (PVTT) in predicting early recurrence (AUC, 0.675 vs 0.523 vs 0.541), and had much higher sensitivity than Barcelona Clinical Liver Cancer (BCLC; 72.0% vs 50.0%), albeit their AUCs were comparable (0.675 vs 0.678). Moreover, combining Clnc with BCLC significantly increased the AUC, compared with Clnc or BCLC alone in predicting early recurrence (all P < 0.05). Finally, logistic and Cox regression analyses suggested that Clnc was an independent prognostic factor and associated with the early recurrence and recurrence-free survival of HCC patients after resection, respectively (all P = 0.001). CONCLUSIONS: Our lncRNA-based classifier Clnc can predict early recurrence of patients undergoing surgical resection of HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a prevalent human malignancy with high morbidity worldwide. Hepatocarcinogenesis is a complex multistep process, and its underlying molecular mechanisms remain largely unknown. Recently, long non-coding RNAs (lncRNAs), a class of newly discovered molecules, have been revealed as essential regulators in the development of HCC. HCC-associated lncRNAs affect multiple malignant phenotypes by modulating gene expression or protein activity. Moreover, the dysregulation of lncRNAs in the liver is also associated with diseases predisposing to HCC, such as chronic viral infection, nonalcoholic steatohepatitis, and liver fibrosis/cirrhosis. A deeper understanding of the lncRNA regulatory network in the multistep processes of HCC development will provide new insights into the diagnosis and treatment of HCC. In this review, we introduce the biogenesis and function of lncRNAs and summarize recent knowledge on how lncRNAs regulate the malignant hallmarks of HCC, such as uncontrolled cell proliferation, resistance to cell death, metabolic reprogramming, immune escape, angiogenesis, and metastasis. We also review emerging insights into the role of lncRNAs in HCC-associated liver diseases. Finally, we discuss the potential applications of lncRNAs as early diagnostic biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]