title: MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer.
abstract: Pancreatic cancer is a highly aggressive malignancy, with <50% patients surviving beyond 6 months after the diagnosis, and thus, there is an urgent need to explore new diagnostic and therapeutic approaches for this disease. Therefore, we conducted microRNA (miRNA) array analysis to detect miRNA molecules potentially associated with pancreatic cancer malignancy. To assess the identified miRNAs, we performed quantitative reverse transcription-PCR on 248 pancreatic ductal adenocarcinomas (UICC stage II). We also examined miRNA expression [microRNA-21 (miR-21) and microRNA-31 (miR-31)] and epigenetic alterations, including CpG island methylator phenotype (CIMP), potentially associated with the identified miRNAs. For functional analysis, we conducted proliferation and invasion assays using a pancreatic cancer cell line. miRNA array analysis revealed that microRNA-196b (miR-196b) was the most up-regulated miRNA in pancreatic cancer tissues compared with normal pancreatic duct cells. High miR-196b expression was associated with miR-21 (P = 0.0025) and miR-31 (P = 0.0001) expression. It was also related to poor prognosis in the multivariate analysis using overall survival (hazard ratio: 1.66; 95% confidence interval: 1.09-2.54; P = 0.019). Functional analysis demonstrated that miR-196b inhibitor decreased cell proliferation and that miR-196b mimic promoted cancer cell invasion. In conclusion, a significant association of high miR-196b expression with poor prognosis was observed in pancreatic cancer. Our data also revealed that miR-196b played an oncogenic role and that the transfection of the miR-196b inhibitor had an anti-tumour effect in the pancreatic cancer cell line. These results suggest that miR-196b is a promising diagnostic biomarker and therapeutic target in pancreatic cancer.
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nosho
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishigami
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Koide
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Mitsuhashi
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shitani
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Motoya
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
authors.forename: Tokuma
authors.initials: T
authors.lastname: Tanuma
authors.affiliation: Department of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maguchi
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan and.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan and.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda 563-0025, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 006-0811, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs