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Hepatic mi R ‐126 is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma
Author(s) -
Ghosh Amit,
Ghosh Alip,
Datta Somenath,
Dasgupta Debanjali,
Das Soumyajit,
Ray Sukanta,
Gupta Subash,
Datta Simanti,
Chowdhury Abhijit,
Chatterjee Raghunath,
Mohapatra Saroj Kant,
Banerjee Soma
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29999
Subject(s) - hepatocellular carcinoma , hepatitis b virus , microrna , cirrhosis , medicine , biomarker , hepatitis b , hepatitis c virus , liver disease , carcinoma , virus , cancer research , gastroenterology , immunology , biology , gene , biochemistry
Controversies about the origin of circulating miRNAs have encouraged us to identify organ specific circulating miRNAs as disease biomarkers. To identify liver‐specific miRNAs for hepatocellular carcinoma (HCC), global expression profiling of miRNAs in liver tissue of HBV‐HCC and HBV‐control with no or mild fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Among ten highly altered miRNAs, six miRNAs were successfully validated in tissues, whereas only two miRNAs, miR‐126 and miR‐142‐3p showed increased expression in plasma of HBV‐HCC compared to HBV‐non‐HCC patients. Subsequently, ROC curve analysis revealed that neither miR‐126 nor miR‐142‐3p performed better than AFP in discriminating HCC from non‐HCC while combination of each with AFP showed significantly higher efficiency rather than AFP alone (AUC: 0.922, 0.908 vs . 0.88; sensitivity: 0.84, 0.86 vs . 0.82 and specificity: 0.92, 0.94 vs . 0.86 respectively). Interestingly, triple combination of markers (miR‐126 + miR‐142‐3p + AFP) showed no additive effect on efficiency (AUC: 0.925) over the dual combination. Again, the expression of only miR‐126 was noticed significantly higher in HBV‐HCC patients with low‐AFP [<250 ng/ml] compared to either non‐HCC or liver cirrhosis (AUC: 0.77, 0.64, respectively). Furthermore, no alteration in expression of mir‐126 in HCV‐HCC or non‐viral‐HCC revealed that miR‐126 + AFP might be specific to HBV‐HCC. To understand the physiological role of these two miRNAs in hepato‐carcinogenesis, target genes related to cancer pathways (APAF1, APC2, CDKN2A, IRS1, CRKL, LIFR, EGR2) were verified. Thus, combination of circulating miR‐126 + AFP is a promising noninvasive diagnostic biomarker for HBV‐HCC and may be useful in the management of HCC patients.