Abstract 4430: Circulating microRNA expression profiles as a novel diagnostic biomarker for esophageal squamous cell carcinoma
Authors: Shimada Yutaka , Takei Yoshinori , Okumura Tomoyuki , Nagata Takuya , Fujinami Haruka , Arima Miwako , Abe Tetsuya , Niwa Yasumasa , Tajika Masahiro , Sudo Tetsuo , Shimizu Kazuharu 
Published: July 2017

Abstract
Background: The findings of a recent analysis on microRNAs (miRNAs) suggest that circulating miRNAs have potential as biomarkers of esophageal squamous cell carcinoma (ESCC). In order to identify specific miRNAs of ESCC, we analyzed the circulating miRNAs of patients who underwent endoscopic mucosal resection (EMR) and esophagectomy. Method: After obtaining written informed consent, we collected paired (pre and post treatment) blood samples from 60 superficial ESCC patients and 42 pretreatment advanced ESCC patients between 2011 and 2015. Samples were divided into training (40 superficial ESCC and 22 advanced ESCC) and test (15 superficial ESCC and 20 advanced ESCC) cohorts according to the period at which they were obtained (between 2011 and 2013 and between 2014 and 2015). Fifty-five patients underwent EMR and were confirmed as stage 0 or Stage 1a. Microarray analyses of blood samples were performed using the 3D-Gene miRNA microarray platform (Toray). Normalization was achieved using the Quantile method, and poor quality samples were excluded from the analysis. Any two clinical groups were compared using a two-sided Student’s t-test. miRNAs exhibiting significant differences were subsequently evaluated using a logistic regression analysis (LRA). Multivariate LRA, Akaike’s Information Criterion (AIC), and Receiver Operating Characteristic (ROC) analyses were performed in order to evaluate the diagnostic power of miRNA combinations. In all series, we used post-EMR patients as control cases.
Results: Twelve miRNAs (miR-6722-5p, 489, 4525, 409-3p, 6088, 3678-5p, 197-5p, 4281, 5090, 3173-3p, 762, and 1470) were selected as discriminant markers (S-combination: AUC 1.00) of superficial ESCC, while 4 miRNAs (miR-4723-3p, 4646-3p, 2392, and 1236-3p) were selected as discriminant markers (A-combination: AUC 1.00) of advanced ESCC in the training cohort. There were no overlap miRNAs between the two combinations. In the test cohort, the S-combination discriminated superficial ESCC (AUC 1.00), while the A-combination discriminated advanced ESCC (AUC 1.00) from post-EMR patients. Furthermore, the S-combination discriminated advanced ESCC in the test cohort (AUC 1.00). However, the A-combination did not clearly discriminate superficial ESCC (AUC 0.833).
Conclusion: Our results suggest that selected miRNAs are useful biomarkers for the discrimination of ESCC. However, biomarkers of superficial ESCC and advanced ESCC may differ.
Citation Format: Yutaka Shimada, Yoshinori Takei, Tomoyuki Okumura, Takuya Nagata, Haruka Fujinami, Miwako Arima, Tetsuya Abe, Yasumasa Niwa, Masahiro Tajika, Tetsuo Sudo, Kazuharu Shimizu. Circulating microRNA expression profiles as a novel diagnostic biomarker for esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4430. doi:10.1158/1538-7445.AM2017-4430