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.
Highlights
Pancreatic cancer is one of the most aggressive cancers and has extremely poor prognosis[1]
Identification of Genes Expressed in pancreatic ductal adenocarcinoma (PDAC)
To identify biomarkers for PDAC, we performed in silico gene expression analysis of PDAC cDNA microarray datasets, using the Oncomine database[33]
Summary
Pancreatic cancer is one of the most aggressive cancers and has extremely poor prognosis[1]. Despite the ambiguity in the panoramic view of human pancreatic ductal adenocarcinoma (PDAC) pathology, accumulating evidence suggests that successive genetic mutations initiate pancreatic cancer[4,5]. K-Ras is frequently mutated in pancreatic cancer (>90%)[14], resulting in hyperactivation of MAPK signaling and subsequent cell hyperproliferation. K-RasG12D oncogenic mutation initiates PanINs6, recapitulating the critical role of K-Ras in the development of human PDAC. More specific and efficient biomarkers are needed to assess pancreatic cancer for early diagnosis and prognosis. Several mutations in KIAA1199 were identified in patients with hearing loss, suggesting that KIAA1199 plays a role in auditory development[26]. KIAA1199 activates Wnt signaling for colorectal cancer cell proliferation[29]. KIAA1199 is a potential biomarker of gastric carcinoma[32]
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