title: Circulating microRNA-196a/b are novel biomarkers associated with metastatic gastric cancer.
abstract: miR-196a and/or miR-196b, involved in cancer initiation and progression, are frequently upregulated in tumour tissues. However, the clinical significance of these microRNAs in gastric cancer (GC) remains to be clarified. In the current study, we investigated the potential utility of circulating miR-196a/b as novel biomarkers for early detection and/or metastatic prognosis of GC. The quantitative real time-polymerase chain reaction data revealed markedly higher pre-operative circulating miR-196a and miR-196b levels in GC patients than healthy controls. Receiver-operating characteristics curve analysis showed that circulating miR-196a, miR-196b and combined miR-196a and miR-196b (miR-196a/b) are more effective than carcinoembryonic antigen or carbohydrate antigen 19-9 alone in distinguishing GC patients from healthy controls, with higher sensitivity and specificity. Circulating miR-196a exhibited higher diagnostic capacity than combined miR-196a/b or miR-196b alone, highlighting its potential as an effective plasma biomarker for GC. In clinicopathological analysis, elevated circulating miR-196a/b levels were highly correlated with metastatic potential or more advanced stages of disease and poorer survival. In addition, the expression levels of circulating miR-196a/b were reduced after surgical resection in GC patients. Taken together, we propose that circulating miR-196a/b serve as a more sensitive and specific novel biomarker than carbohydrate antigen 19-9 for GC monitor, diagnosis and prognosis.
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan, ROC; Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan, ROC.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Tsai
authors.affiliation: Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan, ROC.
authors.forename: Chia-Siu
authors.initials: CS
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, ROC.
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan, ROC; Department of Medical Biotechnology and Laboratory Science, and Graduate Institute of Biomedical Science, Chang Gung University, Taoyuan 333, Taiwan, ROC.
authors.forename: Chung-Guei
authors.initials: CG
authors.lastname: Huang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chia-yi 613, Taiwan, ROC.
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, ROC.
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, ROC.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, ROC.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan, ROC.
authors.forename: Liang-Mou
authors.initials: LM
authors.lastname: Kuo
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, ROC; Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan, ROC.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, ROC; Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan, ROC. Electronic address: khlin@mail.cgu.edu.tw.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000097:blood* / Q000473:pathology / Q000556:secondary*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: Circulating miRNA-196a/b; Diagnosis; Gastric cancer; Metastasis; Prognosis