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

PLOS ONE, Dec 2019

Background Hepatocellular 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. Methods lncRNA 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. Results We 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). Conclusion Our 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).

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144934&type=printable

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

December Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma Kang Wang 0 1 2 Wei xing Guo 0 1 2 Nan Li 0 1 2 Chun fang Gao 0 1 2 Jie Shi 0 1 2 Yu fu Tang 0 1 2 Feng Shen 0 1 2 Meng chao Wu 0 1 2 Shan rong Liu 0 1 2 Shu qun Cheng 0 1 2 0 1 Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China , 2 Changhai Hospital, the Second Military Medical University , Shanghai , China 1 Funding: This work was supported by the grants of the Science Fund for Creative Research Groups (No. 81221061); Chang Jiang Scholars Program (2012); Shanghai Science and Technology Committee (No. 134119a0200); The State Key Project on Infections Diseases of China (2012zx10002016016003); The China National Funds for Distinguished Young Scientists (No. 81125018); The New Excellent Talents Program of Shanghai Municipal Health Bureau (No. XBR2011025); The New Excellent Talents Program of Shanghai Science and Technology Committee (No 2 Editor: Diego Calvisi, University of Medicine , Greifswald, Germany, GERMANY - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Background Hepatocellular 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. Methods lncRNA 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. Results We 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). 10XD1405800); Shanghai Science and Technology Committee (No. 10JC1417600); The National Natural Science Foundation (No. 81101831); Excellent Young Scholar Program of SMMU (No. 20111010B); and Project supported by the Natural Science Foundation of Shanghai, China (No. 12ZR1439600). Competing Interests: The authors have declared that no competing interests exist. Abbreviations: (HCC), Hepatocellular carcinoma; (lncRNAs), long non-coding RNAs; (HBV), hepatitis B virus; (AUC), The area under the receiver operating characteristic curve; (cfCNAs), cell-free circulating nucleic acids; (NCBI), Biotechnology Information; (GEO), Gene Expression Omnibus; (qRT-PCR), quantitative reverse transcription real-time polymerase chain reaction; (ROC), receiver operating characteristic; (ALT), alanine aminotransferase. Conclusion Our 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). Introduction Hepatocellular carcinoma(HCC) is the sixth most common malignancy and has a 5-year overall survival rate of 5–9% [ 1–3 ]. The poor prognosis for this disease primarily results from late detection due to the lack of effective methods for early diagnosis [ 1, 4 ]. Assays for AFP, the traditional serum marker for HCC, are limited by low sensitivity and specificity [ 5–9 ]. Although other molecular markers have been identified for HCC, the heterogeneity of HCC makes early detection a major challenge. Ideally, biomarkers should be accessible in specimens that can be collected conveniently, such as serum or urine. Highly stable cell-free circulating nucleic acids (cfCNAs), which include both RNA and DNA species, have been discovered in human blood, plasma, and urine [ 10 ]. Long non-coding RNAs (lncRNAs) are mRNA-like transcripts that are 200 bp to approximately 100 kb long, map to intronic and intergenic regions[ 11 ], and include subsets of polyadenylated and non-polyadenylated transcripts that differentially accumulate in the nucleus and cytoplasm of cells[ 12, 13 ]. While there is an increasing interest in lncRNAs, to date only a handful has been investigated in HCC, including highly up-regu (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144934&type=printable

Kang Wang, Wei xing Guo, Nan Li, Chun fang Gao, Jie Shi, Yu fu Tang, Feng Shen, Meng chao Wu, Shan rong Liu, Shu qun Cheng. Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma, PLOS ONE, 2015, 12, DOI: 10.1371/journal.pone.0144934