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Published on: March 14, 2019
Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver
Yusuke Yamamoto1, Shunsuke Kondo2, Juntaro Matsuzaki1
1Division of Molecular and Cellular Medicine National Cancer Center Research Institute Tokyo Japan.
Insights
Early detection of hepatocellular carcinoma (HCC) is improved using a novel biomarker model. This model identifies circulating microRNAs (miRNAs) in serum, accurately detecting early-stage HCC with high sensitivity and specificity.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
- High mortality rates are linked to challenges in early HCC detection.
- Existing diagnostic methods often fail to identify HCC in its early stages.
Purpose of the Study:
- To investigate the diagnostic potential of circulating microRNAs (miRNAs) in serum for hepatocellular carcinoma (HCC).
- To develop and validate a diagnostic model for accurate HCC detection, including early stages.
- To improve patient outcomes through enhanced early cancer diagnosis.
Main Methods:
- Serum samples from 345 HCC patients, 46 chronic hepatitis (CH) patients, 93 liver cirrhosis (LC) patients, and 1,033 healthy individuals were analyzed using miRNA microarrays.
- A diagnostic model was constructed based on the expression levels of a combination of eight miRNAs identified in a discovery set.
- The model's diagnostic performance was evaluated in a validation set.
Main Results:
- A diagnostic model comprising eight specific miRNAs demonstrated high accuracy in discriminating HCC from at-risk controls.
- The model achieved an area under the curve (AUC) of 0.99, with 97.7% sensitivity and 94.7% specificity.
- Crucially, the model successfully detected 98% of stage I HCC cases, significantly outperforming conventional methods.
Conclusions:
- Circulating miRNAs show promise as reliable biomarkers for the accurate detection of hepatocellular carcinoma (HCC).
- The developed miRNA-based model offers a highly accurate method for early-stage HCC detection, maintaining diagnostic accuracy even in stage I.
- This approach has the potential to significantly improve patient outcomes by enabling timely diagnosis and treatment.
Abstract:
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. The high mortality rate in HCC is largely due to the difficulty of early detection. In this study, to improve patient outcomes, serum samples from 345 patients with HCC, 46 patients with chronic hepatitis (CH), 93 patients with liver cirrhosis (LC), and 1,033 healthy individuals were analyzed with microRNA (miRNA) microarrays. We investigated the diagnostic potential of circulating miRNAs in serum and developed a detection model of HCC, including early stage. A diagnostic model was constructed based on the expression levels of a combination of miRNAs in a discovery set. We selected 52 miRNAs that had altered expressions according to disease progression status, established the diagnostic model with a combination of eight miRNAs in the discovery set, and tested the model in a validation set. The diagnostic values for discriminating cancer from HCC at-risk control samples were as follows: area under the curve, 0.99; sensitivity, 97.7%; specificity, 94.7%. With this model, 98% of stage I HCC cases were detected; these results were much better than those observed from conventional methods. Conclusion: Circulating miRNAs could serve as biomarkers for the accurate detection of HCC. Because the diagnostic accuracy was maintained even in stage I, this may represent an accurate detection method even for early stage HCC.
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