Development of novel diagnostic system for pancreatic cancer, including early stages, measuring mRNA of whole blood cells

• Published in: Cancer science Vol. 110; no. 4; pp. 1364 - 1388
• Main Authors: Sakai, Yoshio, Honda, Masao, Matsui, Shigeyuki, Komori, Osamu, Murayama, Toshinori, Fujiwara, Tadami, Mizuno, Masaaki, Imai, Yasuhito, Yoshimura, Kenichi, Nasti, Alessandro, Wada, Takashi, Iida, Noriho, Kitahara, Masaaki, Horii, Rika, Toshikatsu, Tamai, Nishikawa, Masashi, Okafuji, Hirofumi, Mizukoshi, Eishiro, Yamashita, Tatsuya, Yamashita, Taro, Arai, Kuniaki, Kitamura, Kazuya, Kawaguchi, Kazunori, Takatori, Hajime, Shimakami, Tetsuro, Terashima, Takeshi, Hayashi, Tomoyuki, Nio, Kouki, Kaneko, Shuichi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2019; John Wiley and Sons Inc
• Subjects: Adenocarcinoma; Aged; Antigens; Biomarkers; Biomarkers, Tumor; Blood; Blood cells; Blood Cells - metabolism; Cancer therapies; clinical trial; Computational Biology - methods; Digestive system; Early Detection of Cancer - methods; Early Detection of Cancer - standards; Female; Gastroenterology; Gene expression; Gene Expression Profiling - methods; Hospitals; Humans; Immunology; in vitro diagnostics; Internal medicine; Male; Medical imaging; Medical prognosis; Medicine; Middle Aged; Molecular Sequence Annotation; mRNA screening system; Neoplasm Staging; Original; pancreas cancer; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Pancreatitis; Reproducibility of Results; Risk Factors; RNA, Messenger - genetics; Sensitivity and Specificity; Software; whole blood cells; United States > US; Switzerland; Japan; clinical trial; in vitro diagnostics; pancreas cancer; whole blood cells; mRNA screening system
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.13971

Pancreatic ductal adenocarcinoma (PDAC) is the most life‐threating disease among all digestive system malignancies. We developed a blood mRNA PDAC screening system using real‐time detection PCR to detect the expression of 56 genes, to discriminate PDAC from noncancer subjects. We undertook a clinical study to assess the performance of the developed system. We collected whole blood RNA from 53 PDAC patients, 102 noncancer subjects, 22 patients with chronic pancreatitis, and 23 patients with intraductal papillary mucinous neoplasms in a per protocol analysis. The sensitivity of the system for PDAC diagnosis was 73.6% (95% confidence interval, 59.7%‐84.7%). The specificity for noncancer volunteers, chronic pancreatitis, and patients with intraductal papillary mucinous neoplasms was 64.7% (54.6%‐73.9%), 63.6% (40.7%‐82.8%), and 47.8% (26.8%‐69.4%), respectively. Importantly, the sensitivity of this system for both stage I and stage II PDAC was 78.6% (57.1%‐100%), suggesting that detection of PDAC by the system is not dependent on the stage of PDAC. These results indicated that the screening system, relying on assessment of changes in mRNA expression in blood cells, is a viable alternative screening strategy for PDAC. Development of a blood mRNA pancreatic ductal adenocarcinoma (PDAC) screening system using real‐time detection PCR in order to discriminate PDAC patients from healthy volunteers. We performed an investigator‐initiated clinical study to assess the performance of the developed system. The sensitivity of the system for PDAC diagnosis and the specificity for non‐cancer volunteers were determined for the evaluation of the screening system.