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PLoS One. 2018 Apr 19;13(4):e0196081. doi: 10.1371/journal.pone.0196081. eCollection 2018.

Optimisation of quantitative miRNA panels to consolidate the diagnostic surveillance of HBV-related hepatocellular carcinoma.

Tat Trung N1,2,3, Duong DC1,4,5, Tong HV3,4,6, Hien TTT1, Hoan PQ1,3, Bang MH2,3, Binh MT2,3,7, Ky TD2, Tung NL2, Thinh NT2, Sang VV3,8, Thao LTP9, Bock CT7,10, Velavan TP3,7,11, Meyer CG3,7,11, Song LH1,3,8, Toan NL3,4.

Author information

1
Department of Molecular Biology, 108 Military Central Hospital, Hanoi, Vietnam.
2
Department of Gastroenterology, 108 Military Central Hospital, Hanoi, Vietnam.
3
Vietnamese-German Center of Excellence in Medical Research, Hanoi, Vietnam.
4
Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
5
Viet Tiep Hospital, Le Chan District, Hai Phong, Vietnam.
6
Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Vietnam.
7
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
8
Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi, Vietnam.
9
Department of Pharmacy, 108 Military Central Hospital, Hanoi, Vietnam.
10
Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
11
Duy Tan University, Dan Nang, Vietnam.

Abstract

BACKGROUND:

Circulating microRNAs (miRNA) are biomarkers for several neoplastic diseases, including hepatocellular carcinoma (HCC). We performed a literature search, followed by experimental screening and validation in order to establish a miRNA panel in combination with the assessment of alpha-fetoprotein (AFP) levels and to evaluate its performance in HCC diagnostics.

METHODS:

Expression of miRNAs was quantified by quantitative PCR (qPCR) in 406 serum samples from 118 Vietnamese patients with hepatitis B (HBV)-related HCC, 69 patients with HBV-related liver cirrhosis (LC), 100 chronic hepatitis B (CHB) patients and 119 healthy controls (HC).

RESULTS:

Three miRNAs (mir-21, mir-122, mir-192) were expressed differentially among the studied subgroups and positively correlated with AFP levels. The individual miRNAs mir-21, mir-122, mir192 or the triplex miRNA panel showed high diagnostic accuracy for HCC (HCC vs. CHB, AUC = 0.906; HCC vs. CHB+LC, AUC = 0.81; HCC vs. CHB+LC+HC, AUC = 0.854). When AFP levels were ≤20ng/ml, the triplex miRNA panel still was accurate in distinguishing HCC from the other conditions (CHB, AUC = 0.922; CHB+LC, AUC = 0.836; CHB+LC+HC, AUC = 0.862). When AFP levels were used in combination with the triplex miRNA panel, the diagnostic performance was significantly improved in discriminating HCC from the other groups (LC, AUC = 0.887; CHB, AUC = 0.948; CHB+LC, AUC = 0.887).

CONCLUSIONS:

The three miRNAs mir-21, mir-122, mir-192, together with AFP, are biomarkers that may be applied to improve diagnostics of HCC in HBV patients, especially in HBV-related LC patients with normal AFP levels or HCC patients with small tumor sizes.

PMID:
29672637
PMCID:
PMC5908085
DOI:
10.1371/journal.pone.0196081
[Indexed for MEDLINE]
Free PMC Article

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