title: A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients.
abstract: Circulating microRNAs (miRNAs) are promising biomarkers for cancer detection. However, multiethnic and multicentric studies of non-small-cell lung cancer (NSCLC) are lacking. We recruited 221 NSCLC patients, 161 controls and 56 benign nodules from both China and America. Initial miRNA screening was performed using the TaqMan Low Density Array followed by confirming individually by RT-qPCR in Chinese cohorts. Finally, we performed a blind trial from an American cohort to validate our findings. RT-qPCR confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214 and miR-7 were significantly elevated in patients compared to controls. The areas under the curve (AUCs) of the ROC curve of this five-serum miRNA panel were 0.976 (95% CI, 0.939-1.0; P < 0.0001) and 0.823 (95% CI, 0.75-0.896; P < 0.0001) for the two confirmation sets, respectively. In the blind trial, the panel correctly classified 95% NSCLC cases and 84% controls from the American cohort. Most importantly, the panel was capable of distinguishing NSCLC from benign nodules with an AUC of 0.979 (95% CI, 0.959-1.0) in the American cohort and allowed correct prediction of 86% and 95% stage I-II tumors in the Chinese and American cohorts, respectively. This serum miRNA panel holds the potential for diagnosing ethnically diverse NSCLC patients.
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Nanjing University, Nanjing, China ; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Nanjing University, Nanjing, China ; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ding
authors.affiliation: Johnson & Johnson Innovation Center Asia Pacific, Shanghai, China.
authors.forename: Mingde
authors.initials: M
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Sidi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Ortho-Clinical Diagnostics, NJ, USA.
authors.forename: Anh
authors.initials: A
authors.lastname: Van Le
authors.affiliation: Ortho-Clinical Diagnostics, NJ, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Soto-Gil
authors.affiliation: Department of Thoracic Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Jiangsu Province Hospital of TCM, Nanjing, China.
authors.forename: Wanjian
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Clinical Laboratory, Nanjing Chest Hospital, Nanjing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Hospital of Xuzhou, Xuzhou, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Nanjing University, Nanjing, China ; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Chunni
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D035683:MicroRNAs
keywords: AUC, the area under the ROC curve; Biomarker; Cq, quantification cycle; Diagnosis; Multicentric; Multiethnic; NSCLC, non-small-cell lung cancer; Non-small-cell lung cancer; RT-qPCR, quantitative reverse transcription polymerase chain reaction; Serum microRNAs; TLDA, TaqMan Low-Density Array; TNM, tumor–node–metastasis; miRNA, microRNA