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Article: Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: A retrospective cohort study
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TitleCirculating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: A retrospective cohort study
 
AuthorsLiu, AM3 1
Yao, TJ1
Wang, W3
Wong, KF3
Lee, NP1
Fan, ST1
Poon, RTP1
Gao, C4
Luk, JM3 1 2
 
Issue Date2012
 
CitationBMJ Open, 2012, v. 2 n. 2, p. e000825 [How to Cite?]
DOI: http://dx.doi.org/10.1136/bmjopen-2012-000825
 
AbstractObjective: Serum α-fetoprotein (AFP) is the most commonly used biomarker for screening hepatocellular carcinoma (HCC) but fails to detect about half of the patients. Thus, we investigated if circulating microRNAs (miRNAs) could outperform AFP for HCC detection. Design: A retrospective cohort study. Setting: Two clinical centres in China. Participants: The exploration phase included 96 patients with HCC who received primary curative hepatectomy, and the validation phase included 29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls. Main outcome measures: Expression of miRNAs was measured by real-time quantitative reverse transcription-PCR. Areas under receiver operating characteristic curves were used to determine the feasibility of using serum miRNA concentration as a diagnostic marker for defining HCC. A multivariate logistic regression analysis was used to evaluate performances of combined serum miRNAs. Results: In the exploration phase, miRNA profiling on resected tumour/adjacent non-tumour tissues identified miR-15b, miR-21, miR-130b and miR-183 highly expressed in tumours. These miRNAs were also detectable in culture supernatants of HCC cell lines and in serum samples of patients. Remarkably, these serum miRNAs were markedly reduced after surgery, indicating the tumour-derived source of these circulating miRNAs. In a cross-centre validation study, combined miR-15b and miR-130b demonstrated as a classifier for HCC detection, yielding a receiver operating characteristic curve area of 0.98 (98.2% sensitivity and 91.5% specificity). The detection sensitivity of the classifier in a subgroup of HCCs with low AFP (<20 ng/ml) was 96.7%. The classifier also identified early-stage HCC cases that could not be detected by AFP. Conclusion: The combined miR-15b and miR-130b classifier is a serum biomarker with clinical value for HCC screening.
 
ISSN2044-6055
2013 Impact Factor: 2.063
2013 SCImago Journal Rankings: 1.078
 
DOIhttp://dx.doi.org/10.1136/bmjopen-2012-000825
 
PubMed Central IDPMC3308260
 
ISI Accession Number IDWOS:000315042100075
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiu, AM
 
dc.contributor.authorYao, TJ
 
dc.contributor.authorWang, W
 
dc.contributor.authorWong, KF
 
dc.contributor.authorLee, NP
 
dc.contributor.authorFan, ST
 
dc.contributor.authorPoon, RTP
 
dc.contributor.authorGao, C
 
dc.contributor.authorLuk, JM
 
dc.date.accessioned2012-08-16T05:59:35Z
 
dc.date.available2012-08-16T05:59:35Z
 
dc.date.issued2012
 
dc.description.abstractObjective: Serum α-fetoprotein (AFP) is the most commonly used biomarker for screening hepatocellular carcinoma (HCC) but fails to detect about half of the patients. Thus, we investigated if circulating microRNAs (miRNAs) could outperform AFP for HCC detection. Design: A retrospective cohort study. Setting: Two clinical centres in China. Participants: The exploration phase included 96 patients with HCC who received primary curative hepatectomy, and the validation phase included 29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls. Main outcome measures: Expression of miRNAs was measured by real-time quantitative reverse transcription-PCR. Areas under receiver operating characteristic curves were used to determine the feasibility of using serum miRNA concentration as a diagnostic marker for defining HCC. A multivariate logistic regression analysis was used to evaluate performances of combined serum miRNAs. Results: In the exploration phase, miRNA profiling on resected tumour/adjacent non-tumour tissues identified miR-15b, miR-21, miR-130b and miR-183 highly expressed in tumours. These miRNAs were also detectable in culture supernatants of HCC cell lines and in serum samples of patients. Remarkably, these serum miRNAs were markedly reduced after surgery, indicating the tumour-derived source of these circulating miRNAs. In a cross-centre validation study, combined miR-15b and miR-130b demonstrated as a classifier for HCC detection, yielding a receiver operating characteristic curve area of 0.98 (98.2% sensitivity and 91.5% specificity). The detection sensitivity of the classifier in a subgroup of HCCs with low AFP (<20 ng/ml) was 96.7%. The classifier also identified early-stage HCC cases that could not be detected by AFP. Conclusion: The combined miR-15b and miR-130b classifier is a serum biomarker with clinical value for HCC screening.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationBMJ Open, 2012, v. 2 n. 2, p. e000825 [How to Cite?]
DOI: http://dx.doi.org/10.1136/bmjopen-2012-000825
 
dc.identifier.doihttp://dx.doi.org/10.1136/bmjopen-2012-000825
 
dc.identifier.epagee000825
 
dc.identifier.hkuros202929
 
dc.identifier.isiWOS:000315042100075
 
dc.identifier.issn2044-6055
2013 Impact Factor: 2.063
2013 SCImago Journal Rankings: 1.078
 
dc.identifier.issue2
 
dc.identifier.pmcidPMC3308260
 
dc.identifier.pmid22403344
 
dc.identifier.scopuseid_2-s2.0-84860141964
 
dc.identifier.spagee000825
 
dc.identifier.urihttp://hdl.handle.net/10722/159926
 
dc.identifier.volume2
 
dc.languageeng
 
dc.relation.ispartofBMJ Open
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.titleCirculating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: A retrospective cohort study
 
dc.typeArticle
 
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<contributor.author>Wang, W</contributor.author>
<contributor.author>Wong, KF</contributor.author>
<contributor.author>Lee, NP</contributor.author>
<contributor.author>Fan, ST</contributor.author>
<contributor.author>Poon, RTP</contributor.author>
<contributor.author>Gao, C</contributor.author>
<contributor.author>Luk, JM</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. Roche RandD Center (China) Ltd.
  3. National University of Singapore
  4. Second Military Medical University