Tumor Markers And Proteomic Studies Of Human Pancreatic Duodenal Juice

Background:Pancreatic cancer is a highly malignant gastrointestinal tumor. Early detection and intervention are quite important in therapy of pancreatic cancer. Comparative proteomics is a useful method for studying of tumor biomarkers. Pancreatic juice is an ideal subject to study pancreatic tumor marker, but it is limited to use in clinical due to its hard to get samples.Objective:To study the feasibility of duodenal fluid substituting for pancreatic juice in the proteomic research of pancreatic cancer. To study the effected factors to the quality of duodenal fluid. To assess the diagnostic value of duodenal fluid CA19-9and CEA in pancreatic cancer.Method:161patients with pancreatic cancer (38patients), benign pancreatic disease (47patients), bile duct disease, ampullary disease (24patients) and other benign gastric disease (52patients) were involved in the study. Duodenal fluids were collected in ERCP and EUS, and proteins were separated by SDS-PAGE. The descriptive statistics was used to evaluate the relationship between affected factors and types of duodenal fluid electrophoresis maps. Proteins in duodenal fluid were analyzed by LC-MS/MS. Duodenal fluid CA19-9and CEA were determined by ELISA.Result:1. Electrophoresis maps of duodenal fluid comprised four types:type I (pancreatic type), type II (gastric type), type III (mixed type) and bile type. The electrophoresis map of type I was similar to which of pancreatic juice.2. Advises of duodenal fluid sample collection:interval of duodenal fluid staying in room temperature and mixture of gastric juice could cause decomposition of proteins. Obstruction of pancreatic duct and bile duct had relationship with mixture of samples. Location of collecting samples, vomiting of patient and suction of gastric juice had no relationship with mixture of samples.3.37proteins were identified in duodenal fluid of pancreatic cancer patient,4differential proteins include Bence-Jones proteins, alpha1-antitrypsin and immunoglobin.4. Duodenal fluid CEA was statistically significant different between pancreatic cancer, which median value was523.6ng/mL, and benign pancreatic disease, which median value was78.7ng/mL(p=0.048). The cutoff value of CEA was390ng/mL, and sensitivity of duodenal fluid CEA in diagnosing pancreatic cancer was60%, and specificity of which was80%. The median value of duodenal fluid CA19-9in pancreatic cancer group (n=8), benign pancreatic diseases group (n=9) and non-pancreatic disease group (n=6) were10375U/mL,9880.1U/mL,185.4U/mL, which was statistically significant different between pancreatic disease and non-pancreatic disease (p=0.005). Conclusion:Duodenal fluid was easy to collect and has similar protein composition of pancreatic juice. It could be substitute for pancreatic juice to be studied in proteomics and tumor biomarker to assist clinical diagnosis. Obstruction of pancreatic duct and bile duct could affect the quality of duodenal fluid, but operation of endoscopy had no effect of quality of duodenal fluid. Alpha1-antitrypsin expressed in duodenal fluid of pancreatic cancer patient, showed relationship with pancreatic cancer.