Computational prediction and experimental validation associating FABP-1 and pancreatic adenocarcinoma with diabetes
نویسندگان
چکیده
BACKGROUND Pancreatic cancer, composed principally of pancreatic adenocarcinoma (PaC), is the fourth leading cause of cancer death in the United States. PaC-associated diabetes may be a marker of early disease. We sought to identify molecules associated with PaC and PaC with diabetes (PaC-DM) using a novel translational bioinformatics approach. We identified fatty acid binding protein-1 (FABP-1) as one of several candidates. The primary aim of this pilot study was to experimentally validate the predicted association between FABP-1 with PaC and PaC with diabetes. METHODS We searched public microarray measurements for genes that were specifically highly expressed in PaC. We then filtered for proteins with known involvement in diabetes. Validation of FABP-1 was performed via antibody immunohistochemistry on formalin-fixed paraffin embedded pancreatic tissue microarrays (FFPE TMA). FFPE TMA were constructed using 148 cores of pancreatic tissue from 134 patients collected between 1995 and 2002 from patients who underwent pancreatic surgery. Primary analysis was performed on 21 normal and 60 pancreatic adenocarcinoma samples, stratified for diabetes. Clinical data on samples was obtained via retrospective chart review. Serial sections were cut per standard protocol. Antibody staining was graded by an experienced pathologist on a scale of 0-3. Bivariate and multivariate analyses were conducted to assess FABP-1 staining and clinical characteristics. RESULTS Normal samples were significantly more likely to come from younger patients. PaC samples were significantly more likely to stain for FABP-1, when FABP-1 staining was considered a binary variable. Compared to normals, there was significantly increased staining in diabetic PaC samples (p = 0.004) and there was a trend towards increased staining in the non-diabetic PaC group (p = 0.07). In logistic regression modeling, FABP-1 staining was significantly associated with diagnosis of PaC (OR 8.6 95% CI 1.1-68, p = 0.04), though age was a confounder. CONCLUSIONS Compared to normal controls, there was a significant positive association between FABP-1 staining and PaC on FFPE-TMA, strengthened by the presence of diabetes. Further studies with closely phenotyped patient samples are required to understand the true relationship between FABP-1, PaC and PaC-associated diabetes. A translational bioinformatics approach has potential to identify novel disease associations and potential biomarkers in gastroenterology.
منابع مشابه
Author's response to reviews Title: Computational Prediction and Experimental Validation Associating FABP-1 and Pancreatic Adenocarcinoma with Diabetes Authors:
متن کامل
Cell-free DNA promoter hypermethylation in plasma as a predictive marker for survival of patients with pancreatic adenocarcinoma
Introduction Few prognostic biomarkers are available for pancreatic cancer. The aim of this study is to examine the correlation between the survival of pancreatic adenocarcinoma patients and hypermethylated genes in plasma-derived cell-free DNA. Methods Consecutive patients with pancreatic adenocarcinoma were prospectively included and staged according to the TNM classification. Methylation-s...
متن کاملUrinary Liver-Type Fatty Acid–Binding Protein and Progression of Diabetic Nephropathy in Type 1 Diabetes
OBJECTIVE Diabetic nephropathy (DN) has mainly been considered a glomerular disease, although tubular dysfunction may also play a role. This study assessed the predictive value for progression of a tubular marker, urinary liver-type fatty acid-binding protein (L-FABP), at all stages of DN. RESEARCH DESIGN AND METHODS At baseline, 1,549 patients with type 1 diabetes had an albumin excretion ra...
متن کاملPancreatic adenocarcinoma in a patient with relapsed Hodgkin’s lymphoma
After curative treatment of Hodgkin’s lymphoma, increased risk of certain solid tumors has been reported. To best of our knowledge this is the first report of metachronous pancreatic adenocarcinoma which developed outside the previous radiation field in a patient with relapse Hodgkin’s lymphoma. Herein we present an 81-year-old female who developed pancreatic adenocarcinoma four yea...
متن کاملExocrine pancreatic adenocarcinoma in a toy breed dog
A 4-year-old female miniature pincher with a 40-day history of weight loss, lethargy and vomiting was referred to Small Animal Hospital, Faculty of Veterinary Medicine, University of Tehran. The case also had severe jaundice, chronic diarrhoea and steatorrhoea. The efforts for saving the life of the case were not successful and finally the animal died of hypovolaemic shock and electrolyte imbal...
متن کامل