Development and validation of an esophageal squamous cell carcinoma detection model by large-scale microrna profiling

Kazuki Sudo, Ken Kato, Juntaro Matsuzaki, Narikazu Boku, Seiichiro Abe, Yutaka Saito, Hiroyuki Daiko, Satoko Takizawa, Yoshiaki Aoki, Hiromi Sakamoto, Shumpei Niida, Fumitaka Takeshita, Takahiro Fukuda, Takahiro Ochiya

研究成果: Article査読

47 被引用数 (Scopus)


IMPORTANCE Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect earlystage ESCC are needed to improve mortality. OBJECTIVE To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. DESIGN, SETTING, AND PARTICIPANTS In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. MAIN OUTCOMES AND MEASURES The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. RESULTS In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4%male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1%male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curvewas 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0%male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7%male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. CONCLUSIONS AND RELEVANCE What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.

ジャーナルJAMA network open
出版ステータスPublished - 2019 5月

ASJC Scopus subject areas

  • 医学一般


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