Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is a common malignancy that has a poor prognosis because there is lack of methods for early diagnosis. We aimed to utilize two serum long non-coding RNAs (lncRNAs), uc001ncr and AX800134, to diagnose hepatitis B virus (HBV)–positive HCC.MethodslncRNA microarrays were utilized to measure the differential expression of lncRNAs between tumor tissues and corresponding non-tumor tissues in HBV-positive hapatocellular carcinoma. uc001ncr and AX800134 were selected as candidate lncRNAs and detected in three independent cohorts containing a total of 684 participants (healthy individuals and chronic HBV patients and HBV-positive HCC patients) who were recruited between March 2011 and December 2012. A logistic regression model was constructed using a training cohort (n = 353) and validated using an independent cohort (n = 181). The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the diagnostic accuracy.ResultsWe determined that a panel based on the expression of uc001ncr and AX800134 accurately diagnosed HBV-positive HCC (AUC values of 0.9494 and 0.9491 for the training and validation cohorts, respectively). The diagnostic performance of the panel remained high in patients with AFP≤400 ng/ml (AUC values of 0.9371 and 0.9527 for the training and validation cohorts, respectively). The panel also diagnosed early HCC (AUC values of 0.9450 and 0.9564 for the training and validation cohorts, respectively).ConclusionOur results indicated that the serum expression of uc001ncr and AX800134 has potential as novel potential biomarker for the diagnosis of HCC, especially in patients with AFP≤400 ng/ml or early-stage disease (BCLC 0+A).

Non-coding RNA in hepatocellular carcinoma: Mechanisms, biomarkers and therapeutic targets

“…Since most protein-based assays lack the desired accuracy, ncRNA-based assays could be considered as an alternative diagnostic tool for HCC. Several studies suggested circulating ncRNAs [142][143][144][145][146][147][148][149][150][151][152][153][154][155] and tumor tissue derived ncRNAs [14][15][16][17]24,156 for HCC diagnosis or survival prediction. While tissue derived ncRNAs might be functionally relevant in the tumor, they are not necessarily good biomarkers for diagnosis.…”

“…However, major limitations of most studies suggesting lncRNAs as HCC biomarkers are the limited cohort sizes and focusing on only one, sometimes two different HCC etiologies. Only four studies analyzed a total of more than 200 patients 142,151,153,154 and very few studies compared more conditions than HCC vs. healthy control. 142,151,154,155,158 Regarding the heterogeneity of HCC, comparisons between HBV/HCV carriers without HCC, cirrhotic liver condition, early HCC, alcohol-induced HCC, and HBV/HCV-associated HCC are necessary to achieve a comprehensive analysis.…”

Long Noncoding RNAs Act as Novel Biomarkers for Hepatocellular Carcinoma: Progress and Prospects

“…Additional serum samples from 61 HBV-positive HCC patients, 60 HBV patients, and 60 healthy individuals were also used to validate the diagnostic efficacy of the two lncRNAs. Based on uc001ncr and AX800134 expression, these lncRNAs were determined to accurately diagnose HBV-positive HCC (AUC = 0.9494), including patients with an AFP of 400 ng/ml (AUC = 0.9371), indicating potential usefulness as biomarkers in diagnosing HCC [ 42 ].…”

The Differential Expression and Possible Function of Long Noncoding RNAs in Liver Cells Infected by Dengue Virus

“…Recently, lncRNAs have been identified to be specifically expressed or function in the infection of HBV, influenza virus, HIV, and enterovirus 71. [32][33][34][35] There is evidence to show that dynamic changes in chromatin, chromosomes, and nuclear architecture are regulated by lncRNAs. 36 Recent studies have shown that the expression levels of host lncRNAs are changed in response to virus infection.…”