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.
Highlights
Pancreatic cancer is one of the most lethal cancers
The five-year survival rate for patients with exocrine pancreatic cancer is estimated at 14% for stage IA, but it drops to 1% for stage IV [1]
All other patients with pancreatic cancer who did not undergo surgical resection were classified as cStage III or IV
Summary
Pancreatic cancer is one of the most lethal cancers. Most pancreatic cancers do not accompany any particular clinical symptoms in the early stage, permitting the cancers to progress undetected. The anatomical location of the pancreas, deep in a retroperitoneal space surrounded by many other organs, hinders the acquisition of a biopsy. All of these factors prevent the early detection of pancreatic cancer. Because the most promising treatment for pancreatic cancer is surgical resection, detecting pancreatic cancer at surgically resectable stages is crucial for improving the survival rate of patients with pancreatic cancer. From this point of view, the screening of the early stages of pancreatic or biliary-tract cancers is imperative
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