MedWire News: A seven-marker microRNA panel accurately distinguishes patients with hepatitis B virus (HBV)-related hepatocellualar carcinoma (HCC) from those with chronic hepatitis B or cirrhosis, and also from healthy individuals without liver dysfunction, research shows.
"Our study demonstrates that this plasma microRNA panel has considerable clinical value for the early diagnosis of HCC, so that more patients, who would have otherwise missed the curative treatment window, can benefit from the optimal therapy," say Jia Fan (Fudan University, Shanghai, China) and colleagues.
The researchers note, in the Journal of Clinical Oncology, that more than 60% of patients with HCC do not receive curative therapy as a result of late clinical presentation and diagnosis.
"Discovery of an effective and reliable tool for early diagnosis of HCC would play a pivotal role in improving the prognosis of patients with HCC," they write.
Since many studies have demonstrated that microRNA expression profiles in HCC and normal tissue are significantly different, Fan and team investigated whether plasma microRNAs can be used to detect HBV-related HCC.
The evaluated plasma microRNA expression over three phases in a total of 934 participants who had HBV-related HCC, chronic hepatitis B, cirrhosis, or were healthy.
In the discovery phase, the researchers used microarray technology to screen 137 samples for 723 microRNAs. This process identified 15 microRNAs that were significantly differentially expressed between the participants with HBV-related HCC, and those who were healthy or had chronic hepatitis B or cirrhosis (controls).
Expression of these microRNAs was then measured by quantitative reverse-transcriptase polymerase chain reaction in an independent cohort of 102 plasma samples.
Seven of the microRNAs (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a, and miR-801) had significantly different expression levels between the HBV-related HCC group and the three control groups. These were tested in a further 305 samples that, together with the 102 previous samples, comprised the training cohort.
The area under the receiver operating characteristic curve (AUC) - a measure of diagnostic accuracy - for the detection of HBV-related HCC using the microRNA panel was 0.864 in the training cohort. The panel had a sensitivity of 68.6% and a specificity of 90.1%
In an independent validation cohort of 390 samples, the AUC for the microRNA panel was 0.852, sensitivity was 81.1%, and specificity was 83.5%.
The "satisfactory diagnostic performance" of the microRNA panel persisted regardless of disease status, with AUCs of 0.888, 0.888, 0.901, and 0.881 for Barcelona Clinic Liver Cancer stages 0, A, B, and C, respectively.
The researchers also evaluated the performance of the microRNA panel in differentiating the HBV-related HCC group from each of the three control groups.
The analysis demonstrated that the panel had high accuracy in discriminating HCC from healthy people (AUC=0.941), and from those with chronic hepatitis B (AUC=0.842) or cirrhosis (AUC=0.884).
This study shows that that plasma miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a, and miR-801 are potential circulating markers for diagnosing HCC, Fan and co-authors conclude.
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