Molecular Profiles Aid Diagnosis of Hepatitis Infections

The detection of specific biomarkers in the serum of patients with suspected liver disease will help define the causative agent.

Expression profiles of micro ribonucleic acids (miRNAs) in serum can serve as a subset of molecular markers for the diagnosis of Hepatitis B virus (HBV) infection and HBV-positive hepatocellular carcinoma (HCC).

In a study carried out in Nanjing University, (Nanjing, China), 513 subjects were recruited, of whom 210 were controls, 135 were infected with HBV, 48 had Hepatitis C virus (HCV), and 120 HCC-affected individuals. A strategy of initial screening was done by Solexa sequencing (San Diego, CA, USA) followed by validation with quantitative reverse transcription-PCR (qRT-PCR) assay. As there is a close link between chronic hepatitis B and HCC, the scientists compared miRNA expression profiles in HBV serum with that in control serum and successfully obtained 13 miRNAs that were differentially expressed in HBV serum.

The 13-miRNA-based biomarker accurately discriminated not only HBV cases from controls and HCV cases, but also HBV-positive HCC cases from control and HBV cases. By directly comparing miRNA expressions in HCC serum with those in controls, they identified six miRNAs that were significantly upregulated in HCC samples. Two of these miRNAs, miR-375 and miR-92a, were also identified as HBV specific. Three of these miRNAs (miR-25, miR-375, and let-7f) could be employed as biomarkers, as they clearly separate HCC cases from controls.

The study demonstrates for the first time that serum miRNA profiles can serve as novel and noninvasive biomarkers for HBV infection and HBV-positive HCC diagnosis. The strategy of using Solexa sequencing followed by quantatative RT-PCR validation provides a successful approach to identifying serum miRNA profiles as biomarkers for the diagnosis of various diseases. The study was published online on November 23, 2010 in Cancer Research.

Related Links:
Nanjing University
Illumina