Identification of KIAA1199 as a Biomarker for Pancreatic Intraepithelial Neoplasia

Abstract

Pancreatic cancer is one of the most aggressive cancers and has an extremely poor prognosis. Despite recent progress in both basic and clinical research, most pancreatic cancers are detected at an incurable stage owing to the absence of disease-specific symptoms. Thus, developing novel approaches for detecting pancreatic cancer at an early stage is imperative. Our in silico and immunohistochemical analyses showed that KIAA1199 is specifically expressed in human pancreatic cancer cells and pancreatic intraepithelial neoplasia, the early lesion of pancreatic cancer, in a genetically engineered mouse model and in human patient samples. We also detected secreted KIAA1199 protein in blood samples obtained from pancreatic cancer mouse models, but not in normal mice. Furthermore, we found that assessing KIAA1199 autoantibody increased the sensitivity of detecting pancreatic cancer. These results indicate the potential benefits of using KIAA1199 as a biomarker for early-stage pancreatic cancer.

Central Role of CEMIP in Tumorigenesis and Its Potential as Therapeutic Target

“…Despite the majority trend of over-expression of CEMIP observed in many cancer, a series of experiments in breast cancer reversely provided evidence through inhibition of tumor proliferation, adhesion, tumor angiogenesis and migration meanwhile accelerated apoptosis happened when CEMIP was absent 28 . In pancreatic ductal adenocarcinoma, over-expressed CEMIP alerted an aggressive tumor progression and early mortality 26 , 29 , 30 . Due to the secretion ability of CEMIP, high CEMIP level could be detected in cancer patients' blood, and the blood CEMIP positively correlated to grade of tumor malignancy.…”

“…Due to the secretion ability of CEMIP, high CEMIP level could be detected in cancer patients' blood, and the blood CEMIP positively correlated to grade of tumor malignancy. According to the report, detection of CEMIP could avoid the false positive result which was caused by carbohydrate antigen marker detection 30 . Among variety of cancer tissues, over-expression of CEMIP was commonly observed existed, especially in the late stage accompanying with dissemination.…”

Combined use of CEMIP and CA 19-9 enhances diagnostic accuracy for pancreatic cancer

“…demonstrated its association with prognosis in pancreatic cancer 10 . However, the sample sizes of these previous studies were too small to draw a solid conclusion 10 , 16 , 17 . On the other hand, despite its limitations, CA 19-9 has been proposed as a diagnostic tool for the detection of pancreatic cancer.…”

“…Recently, several studies have investigated the role of CEMIP in pancreatic cancer; CEMIP has been reported to be associated with early detection, cancer cell migration, invasion, and poor prognosis in previous studies 10 , 16 , 17 . Suh et al .…”

“…Suh et al . suggested that CEMIP may be useful for detecting pancreatic cancer at an early stage 16 , while Koga et al . demonstrated its association with prognosis in pancreatic cancer 10 .…”