Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarcinoma

Reiko Takayama, Hidewaki Nakagawa, Akira Sawaki, Nobumasa Mizuno, Hiroki Kawai, Masahiro Tajika, Yasushi Yatabe, Keitaro Matsuo, Rie Uehara, Ken Ichiro Ono, Yusuke Nakamura, Kenji Yamao

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35 Citations (Scopus)

Abstract

Background and Aims: Serum biomarkers for the early detection of pancreatic cancer are not currently available. We evaluated the usefulness of a novel serum marker, REG4, in the diagnosis of pancreatic cancer, as compared to carbohydrate antigen (CA) 19-9. Methods: We collected pretherapeutic sera from 92 patients with pancreatic cancer, as well as sera from 28 patients with other pancreatic tumors, 11 patients with pancreatitis, and 69 healthy controls. Serum levels of REG4 were measured using a standard sandwich enzyme-linked immunosorbent assay (ELISA). Results: Compared with healthy controls, serum levels of REG4 were higher in pancreatic cancer patients (P < 0.001), and in patients with pancreatitis (P < 0.001). Receiver operating characteristic (ROC) analysis indicated that serum REG4 performed better than serum CA19-9 for distinguishing patients with pancreatic cancer from healthy controls [areas under the curve (AUC) for REG4 and CA19-9 were 0.922 and 0.884, respectively]. When we validated the study, the sensitivity of REG4 for pancreatic cancer was 94.9%, specificity was 64.0%, and accuracy was 77.5% for the REG4 cutoff value of 3.49 ng/ml. No correlation was seen between serum REG4 and CA19-9 levels, with the sensitivity, specificity, and accuracy of the combined markers reaching 100.0, 60.0, and 77.5%, respectively. No significant differences were seen among any stages of pancreatic cancer. In surgical specimens, immunohistochemical analysis found a correlation between serum REG4 levels and REG4 expression in pancreatic cancers. Conclusions: REG4 is expressed in pancreatic cancer, and serum levels of REG4 offer a useful indicator for distinguishing between patients with pancreatic cancer and healthy subjects. Serum REG4 has potential for use as a screening serum marker for pancreatic cancers, including early-stage cancers.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalJournal of Gastroenterology
Volume45
Issue number1
DOIs
Publication statusPublished - 01-01-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Takayama, R., Nakagawa, H., Sawaki, A., Mizuno, N., Kawai, H., Tajika, M., Yatabe, Y., Matsuo, K., Uehara, R., Ono, K. I., Nakamura, Y., & Yamao, K. (2010). Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarcinoma. Journal of Gastroenterology, 45(1), 52-59. https://doi.org/10.1007/s00535-009-0114-y