Abstract 3122: A strategy for detecting high-risk groups for pancreatic cancer with glycol-biomarkers

Abstract

Abstract (Aim) Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers, showing a high potential for invasive activity and high recurrence rates. One of the reasons for poor prognosis of PDAC is a difficulty in an early diagnosis. When pancreatic tumors are detected by CT or MRI examinations, most cases are at the advanced stage even if tumor size is within 2 cm. To make an early diagnosis for PDAC truely, we should make a targeting of high-risk groups for developing PDAC like chronic hepatitis followed by hepatocellular carcinoma. Aberrant glycosylation is a promising target for cancer biomarkers. Several kinds of glyco-biomarkers are clinically used for PDAC diagnosis like CA19-9. We have reported that fucosylated haptoglobin (Fuc-Hpt) is a novel type of glyco-biomarker for PDAC. Serum Fuc-Hpt levels are dramatically increased at the stage IV of PDAC as well as a few cases of Stage I-III. In the present study, we performed pathological analysis of surrounding tissues around pancreatic cancer as well as normal pancreas in autopsy cases and investigated the clinical usefulness of glycol-biomarkers for chronic pancreatitis and pancreatic cancer (Subjects and Methods) 88 cases of pancreatic cancer patients and 100 cases of other diseases are enrolled in this study. Inflammation, fibrosis and fatty changes were investigated in these pancreatic tissues by 2 independent researchers in blind way. Serum fucosylated haptoglobin (Fuc-Hpt) levels in patients with chronic pancreatitis and pancreatic cancer were measured with lectin-antibody ELISA, using Aleuria aurantia lectin (AAL) and Pholiota squarrosa lectin (PhoSL). AAL recognizes all types of fucosylation and PhoSL recognizes core fucosylation. (Results) Pancreatectomy specimens showed a higher ratio of positive change in fibrosis (86% vs. 42%), fatty degeneration (72% vs. 44%), and inflammatory cell infiltration (14% vs. 3%) than control samples. Multivariate analyses demonstrated that each histological change was a significant, independent determinant for PDAC. In contrast, AAL-reactive Fuc-Hpt levels were increased in patients with pancreatic cancer and AAL-reactive Fuc-Hpt was though to be produced in the liver metastasis of pancreatic cancer. In contrast, PhoSL-reactive Fuc-Hpt levels were increased in patients with chronic pancreatitis, compared to pancreatic cancer. Correlations of PhoSL-reactive Fuc-Hpt levels and other biochemical parameters such as serum amylase, lipase, and elastase levels were not observed. The investigation of mechanisms underlying an increase of serum PhoSL-reactive Fuc-Hpt in patients with chronic pancreatitis is underway. (Conclusion) Cryptogenic pancreatitis might be a premalignant disease for pancreatic cancer and dramatic changes in fucosylation linkage on Fuc-Hpt were observed in pancreatic carcinogenesis. These findings give us a possibility of preventing or diagnosing pancreatic cancer at earlier stage, chronic pancreatitis. Citation Format: Eiji Miyoshi, Tomohiro Maekawa, Makiko Ueda, Mayuka Shimomura, Shinji Takamatsu, Kotarosumitomo Nakayama, Yoshihiro Kamada, Yasuhiko Tomita. A strategy for detecting high-risk groups for pancreatic cancer with glycol-biomarkers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3122.