Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver Disease

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...

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Published inHepatology communications Vol. 4; no. 2; pp. 284 - 297
Main Authors Yamamoto, Yusuke, Kondo, Shunsuke, Matsuzaki, Juntaro, Esaki, Minoru, Okusaka, Takuji, Shimada, Kazuaki, Murakami, Yoshiki, Enomoto, Masaru, Tamori, Akihiro, Kato, Ken, Aoki, Yoshiaki, Takizawa, Satoko, Sakamoto, Hiromi, Niida, Shumpei, Takeshita, Fumitaka, Ochiya, Takahiro
Format Journal Article
LanguageEnglish
Published United States Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.02.2020
John Wiley and Sons Inc
Wolters Kluwer Health/LWW
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Summary: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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These authors contributed equally to this work.
Potential conflict of interest: Dr. Kondo received grants from MSD, Pfizer, ASLAN, Takeda, Eli Lilly, and Boehringer Ingelheim. Dr. Okusaka received grants from Bristol Myers Squibb K.K. Dr. Takizawa is an employee of Toray Industries, Inc. The other authors have nothing to report.
Supported by the Japan Agency for Medical Research and Development through a “Development of Diagnostic Technology for Detection of miRNA in Body Fluids” grant (number 16AE0101011H0003 to T.Oc.).
ISSN:2471-254X
2471-254X
DOI:10.1002/hep4.1451