A six-microRNA signature in plasma was identified as a potential biomarker in diagnosis of esophageal squamous cell carcinoma

// Xin Zhou 1, * , Wei Wen 2, * , Jun Zhu 3, * , Zebo Huang 1 , Lan Zhang 1 , Huo Zhang 1 , Lian-Wen Qi 4 , Xia Shan 5 , Tongshan Wang 1 , Wenfang Cheng 6 , Danxia Zhu 7 , Yin Yin 8 , Yan Chen 9 , Wei Zhu 1 , Yongqian Shu 1, 10 , Ping Liu 1, 10 1 Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China 2 Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China 3 Department of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing 210009, PR China 4 State Key Laboratory of Natural Medicines and Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210009, PR China 5 Department of Respiration, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 210000, PR China 6 Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China 7 Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, PR China 8 Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China 9 Department of Emergency, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China 10 Cancer Center of Nanjing Medical University, Nanjing 210029, PR China * These authors contributed equally to this work Correspondence to: Wei Zhu, email: zhuwei@njmu.edu.cn Ping Liu, email: liu-ping@csco.org.cn Keywords: miRNA, esophageal squamous cell carcinoma, diagnosis, exosomes, TCGA Received: October 25, 2016      Accepted: March 15, 2017      Published: March 23, 2017 ABSTRACT The differential expression of microRNAs (miRNAs) in plasma of esophageal squamous cell carcinoma (ESCC) patients may serve as a diagnostic biomarker. A four-stage study was conducted to identify plasma miRNAs with potential in detecting ESCC. Exiqon panels (2 ESCC pools vs. 1 normal control (NC) pool) were applied in the screening phase to obtain miRNA profiles. The identified miRNAs were further evaluated through training (36 ESCC VS. 42 NCs) and testing stages (101 ESCC VS. 113 NCs) with qRT-PCR assays. A six-miRNA signature including up-regulated miR-106a, miR-18a, miR-20b, miR-486-5p, miR-584 and down-regulated miR-223-3p in ESCC was identified. The signature could accurately discriminate ESCC patients from NCs with areas under the receiver operating characteristic curve of 0.935, 0.959 and 0.966 for the training, testing and the additional validation stage (41 ESCC VS. 50 NCs), respectively. MiR-106a and miR-584 were significantly up-regulated in tumor tissues with qRT-PCR assays. And miR-584 was also up-regulated in ESCC tissues from TCGA database. In addition, exosomal miR-223-3p and miR-584 were consistently dysregulated with those in plasma and could also act as biomarkers in diagnosis of ESCC. In conclusion, we identified a six-miRNA signature in plasma which could act as a non-invasive biomarker in detection of ESCC.