MiRNA Flags Preclinical Hepatocellular Carcinoma

Patients at risk for liver cancer may benefit from a microRNA screening test

medwireNews: Screening for circulating microRNA (miRNA) can detect preclinical and clinical hepatocellular carcinoma (HC) in at-risk patients, suggests research published in The Lancet Oncology.

“The miRNA classifier could be valuable to detect preclinical hepatocellular carcinoma, providing patients with a chance of curative resection and longer survival”, say Shi-Mei Zhuang, from Sun Yat-sen University in Guangzhou, China, and co-authors.

The team created a serum classifier based on seven miRNAs differentially expressed in a group of 257 healthy individuals and patients with HC, chronic hepatitis B or liver cirrhosis.

The test was more accurate than a 20 ng/mL threshold of α-fetoprotein (AFP20) for separating individuals with and without HC in two validation cohorts of healthy controls, patients with chronic hepatitis B, liver cirrhosis, and inactive hepatitis B antigen carriers (n=352 and 139).

The classifier was also shown to be more sensitive than AFP20 to detect HC at the time of diagnosis in these three cohorts and a fourth cohort of 162 hepatitis B-positive patients on an HC surveillance programme, with a range of 70.4% to 85.7% versus 40.7% to 69.4%. And the classifier had comparable specificity to AFP20, with a range of 80.0% to 91.1% versus 84.9% to 100.0%.

The fourth cohort formed the basis of a nested case–control study and included 27 patients who were diagnosed with HC and 135 matched controls, the researchers explain.

The classifier detected HC in 29.6% of the cases 12 months before clinical diagnosis using two imaging techniques, rising to 48.1% at 9 and 6 months before, and 55.6% at 3 months before clinical diagnosis. By contrast, the sensitivity of AFP20 was just 7.4%, 11.1%, 18.5% and 22.2% at these time points.

Moreover, the classifier was better able than AFP20 to detect both small-size HC and early-stage HC, and also identified HC in patients who tested negative for AFP.

“[T]he miRNA classifier… offers promising diagnostic accuracy and constitutes the proof of concept that miRNA profiling could be an accepted strategy for early diagnosis”, writes Alejandro Forner, from the University of Barcelona in Spain, in an accompanying comment.

Noting that AFP has a very poor performance for early HC detection, however, he says that there is “still room for improvement” before the miRNA classifier can be considered “an acceptable screening method”.

In particular, Alejandro Forner observes that it “is unclear whether increases of miRNA classifier levels are associated with or caused by the tumour itself, rather than the related clinical or biochemical profile of underlying causes such as cirrhosis.”

Thus, validation studies are required to determine the impact of related factors, such as liver dysfunction, hepatitis virus and alcohol, on the utility of the miRNA classifier, he concludes.


Lin X-J, Chong Y, Guo Z-W, et al. A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study. Lancet Oncol 2015; Advance online publication 15 June. DOI: dx.doi.org/10.1016/S1470-2045(15)00048-0

Forner A. Hepatocellular carcinoma surveillance with miRNAs. Lancet Oncol 2015; Advance online publication 15 June. DOI: dx.doi.org/10.1016/S1470-2045(15)00014-5

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