Five serum microRNAs for detection and predicting of ovarian cancer

Abstract

Five serum microRNAs for detection and predicting of ovarian cancer Weiwei Wanga,1, Li-rong Wub,1, Chunyu Lic,1, Xin Zhoud, Ping Liud, Xuemei Jiae,***, Yan Chenc,f,**, Wei Zhud,g,* a Intensive Care Unit, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China b Department of Radiation Oncology, The Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting Road, Nanjing 210009, China c Emergency Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China d Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China e Department of Obstetrics and Gynecology, Nanjing Maternity and Child Health Care hospital, 123 Mochou Road, Nanjing 210004, China f Medical Department, Kizilsu Kirghiz Autonomous Prefecture People’s Hospital, Artux 845350, China g Department of Oncology, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, No.1399 West Road, Shengze Town, Wujiang District, Suzhou 215000, China A R T I C L E I N F O Article history: Received 14 November 2018 Received in revised form 24 March 2019 Accepted 31 March 2019 Available online 6 April 2019 Keywords: microRNA Ovarian cancer Biomarker Detection Prediction qRT-PCR A B S T R A C T Objective: Ovarian cancer (OC) was one of the deadliest gynecological malignancy among women in global. Serum microRNAs (miRNAs) could serve as promising diagnostic biomarkers for patients with OC. Study design: Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel, we identified 27 differentially expressed miRNAs from one normal control (NC) pool and two OC pool samples in the initial screening stage. We further verified the miRNAs in the training (30 OC VS. 36 NCs) and validation stages (80 OC VS. 80 NCs) based on qRT-PCR. Later, the expression levels of the identified miRNAs were also evaluated in exosomes and tissues. Results: We found a serum microRNA signature including five overexpressed miRNAs (miR-200c-3p, miR- 346, miR-127-3p, miR-143-3p and miR-205-5p) in OC in comparison with NCs. The areas under the receiver operating characteristic (ROC) curve (AUC) of the five-miRNA panel were 0.783 for the training stage and 0.745 for the validation stage. The diagnostic sensitivity and specificity of the combined fivemiRNA panel was 0.818 and 0.609 when the cut-off value was 0.636. The levels of miR-200c-3p, miR-346 and miR-127-3p in serum were related to tumor grade and distant metastasis of OC. The expression levels of the five miRNAs were also significantly up-regulated in serum exosomes (32 OC VS. 32 NCs). Furthermore, miR-200c-3p was significantly elevated in OC tissues (22 OC VS. 22 NCs). But the levels of the miR-346 and miR-143-3p were significantly lower in OC tissues. Conclusion: Our findings showed a five-miRNA panel in serum for the detection of OC. Moreover, serum expression levels of miR