TY - JOUR
T1 - Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver Disease
AU - Yamamoto, Yusuke
AU - Kondo, Shunsuke
AU - Matsuzaki, Juntaro
AU - Esaki, Minoru
AU - Okusaka, Takuji
AU - Shimada, Kazuaki
AU - Murakami, Yoshiki
AU - Enomoto, Masaru
AU - Tamori, Akihiro
AU - Kato, Ken
AU - Aoki, Yoshiaki
AU - Takizawa, Satoko
AU - Sakamoto, Hiromi
AU - Niida, Shumpei
AU - Takeshita, Fumitaka
AU - Ochiya, Takahiro
N1 - Funding Information:
We thank Tomomi Fukuda, Takumi Sonoda, Hiroko Tadokoro, Tatsuya Suzuki, Junpei Kawauchi, Satoshi Kondou, Makiko Ichikawa, and Kamakura Techno-Science, Inc. for performing the microarray assays. We also thank Noriko Abe, Michiko Ohori, and Takumi Sonoda for collecting samples from the freezing room and Kazuki Sudo for independent confirmation of participant eligibility. Some of the samples and clinical information used in this study were obtained from the NCC Biobank, which is supported by National Cancer Center Research and Development Fund (29-A-1). We also thank the NCGG Biobank for providing the biological resources.
Publisher Copyright:
© 2019 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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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U2 - 10.1002/hep4.1451
DO - 10.1002/hep4.1451
M3 - Article
AN - SCOPUS:85084553650
SN - 2471-254X
VL - 4
SP - 284
EP - 297
JO - Hepatology Communications
JF - Hepatology Communications
IS - 2
ER -