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MicroRNA Blood Test May Help Diagnose Early Liver Cancer in People with Hepatitis B

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A set of 7 microRNAs in blood plasma accurately diagnosed hepatocellular carcinoma (HCC) and could distinguish between liver cancer and cirrhosis among people with chronic hepatitis B, according to study findings reported in the November 21, 2011, advance online edition of the Journal of Clinical Oncology.

Over years or decades chronic hepatitis B virus (HBV) infection can lead to serious liver damage including advanced fibrosis, cirrhosis, and HCC (a form of primary liver cancer). Unfortunately, a majority of people with HCC -- many of whom are unaware they even have hepatitis B -- are diagnosed at later stages when treatment is less likely to be successful.

Jian Zhou from the Liver Cancer Institute of Fudan Universityin Shanghai and colleagues aimed to identify plasma microRNAs -- short sequences of single-strand RNA genetic material detectable in the blood -- that could be used to diagnose HBV-related HCC.

The analysis included 934 participants divided into 4 groups: healthy people without hepatitis B, chronic hepatitis B patients, people with cirrhosis, and patients with HBV-related HCC.

The researchers used a microarray method to screen 723 microRNAs in 137 plasma samples. A quantitative polymerase chain reaction (PCR) assay was then used to evaluate the expression of selected microRNAs. One set of data was used as a training set to identify relevant microRNAs, then another set was used to validate the findings.

Results

  • A panel of 7 microRNAs -- miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a, and miR-801 -- provided high diagnostic accuracy for detecting HCC.
  • AUC (a measure of diagnostic accuracy with a maximum level of 1.0) was 0.864 for the training data set and 0.888 for the validation data set.
  • The diagnostic performance of the microRNA panel was satisfactory regardless of HCC disease status.
  • The microRNA panel could also distinguish patients with HCC from healthy participants, those with chronic hepatitis B, and those with cirrhosis.
  • miR-26a, which has been linked to HCC and survival in prior studies, did not have satisfactory diagnostic accuracy as a single marker.

Based on these findings, the study authors concluded, "We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC."

Thus, they added, "patients who would have otherwise missed the curative treatment window can benefit from optimal therapy."

In an accompanying editorial, Chien-Jen Chen and Mei-Hsuan Lee from the Academia Sinica Genomics Research Center in Taipei noted that about half of human microRNAs are located in fragile regions of chromosomes, which are associated with the development of cancer; some microRNAs have been linked to tumor suppression and oncogenesis (development of cancer).

They suggested that while existing liver cancer screening methods including alpha fetoprotein (AFP) and MRI or ultrasound imaging are not optimal, combining these methods with microRNAs may improve detection of early HCC.

Investigator affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Institute of Biomedical Sciences, Fudan University; Shanghai Public Health Clinic Center; Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Bringham and Women's Hospital, Harvard Medical School, Boston, MA.

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References

J Zhou, L Yu, X Gao, et al. Plasma MicroRNAPanel to Diagnose Hepatitis B Virus–Related Hepatocellular Carcinoma. Journal of Clinical Oncology. November 21, 2011 (Epub ahead of print).

CJ Chen. Early Diagnosis of Hepatocellular Carcinoma by Multiple MicroRNAs: Validity, Efficacy, and Cost-Effectiveness. Journal of Clinical Oncology. November 21, 2011 (Epub ahead of print).