title: MicroRNA markers for the diagnosis of pancreatic and biliary-tract cancers.
abstract: It is difficult to detect pancreatic cancer or biliary-tract cancer at an early stage using current diagnostic technology. Utilizing microRNA (miRNA) markers that are stably present in peripheral blood, we aimed to identify pancreatic and biliary-tract cancers in patients. With "3D-Gene", a highly sensitive microarray, we examined comprehensive miRNA expression profiles in 571 serum samples obtained from healthy patients, patients with pancreatic, biliary-tract, or other digestive cancers, and patients with non-malignant abnormalities in the pancreas or biliary tract. The samples were randomly divided into training and test cohorts, and candidate miRNA markers were independently evaluated. We found 81 miRNAs for pancreatic cancer and 66 miRNAs for biliary-tract cancer that showed statistically different expression compared with healthy controls. Among those markers, 55 miRNAs were common in both the pancreatic and biliary-tract cancer samples. The previously reported miR-125a-3p was one of the common markers; however, it was also expressed in other types of digestive-tract cancers, suggesting that it is not specific to cancer types. In order to discriminate the pancreato-biliary cancers from all other clinical conditions including the healthy controls, non-malignant abnormalities, and other types of cancers, we developed a diagnostic index using expression profiles of the 10 most significant miRNAs. A combination of eight miRNAs (miR-6075, miR-4294, miR-6880-5p, miR-6799-5p, miR-125a-3p, miR-4530, miR-6836-3p, and miR-4476) achieved a sensitivity, specificity, accuracy and AUC of 80.3%, 97.6%, 91.6% and 0.953, respectively. In contrast, CA19-9 and CEA gave sensitivities of 65.6% and 40.0%, specificities of 92.9% and 88.6%, and accuracies of 82.1% and 71.8%, respectively, in the same test cohort. This diagnostic index identified 18/21 operable pancreatic cancers and 38/48 operable biliary-tract cancers in the entire cohort. Our results suggest that the assessment of these miRNA markers is clinically valuable to identify patients with pancreato-biliary cancers who could benefit from surgical intervention.
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.affiliation: New Frontiers Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sudo
authors.affiliation: New Frontiers Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Kawauchi
authors.affiliation: New Frontiers Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Takizawa
authors.affiliation: New Projects Development Division, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondou
authors.affiliation: New Projects Development Division, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nobumasa
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000368:Aged; D001661:Biliary Tract Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs