Our institution performed pancreatectomy with autologous islet transplantation (AIT) in 89 patients with chronic pancreatitis since 2000. To identify biomarkers distinctive to chronic pancreatitis (CP) that might relate to AIT outcomes, we have sought to characterize gene expression signatures. Purified RNA samples were obtained from 4 CP patients (2 idiopathic, 1 hereditary CF mutation and 1 alcoholic), 2 normal pancreas and 3 islet preparations, and a variety of non-islet, non-pancreatitic human tissues. Standard Affymetrix GeneChip protocols were used for RNA labeling, hybridization, and scanning. “.CEL” files were generated using Affymetrix GCOS software (version 1.4) and were subjected to RNA normalization (Irizarry et al. 2004) as implemented in GeneSpring 7.3. Gene expression was referenced relative to the mean of normal pancreas samples. Student's t-test was used to identify genes consistently up or down-regulated in the CP samples relative to normal pancreas and in islet preparations relative to whole pancreas and other tissue and cell preparations. In the samples from the 4 CP patients, 499 genes were identified as consistently overexpressed or underexpressed relative to the normal samples. Genes whose expression was most decreased and increased in the diseased pancreas are listed below. All 4 patients were glucose intolerant prior to surgery; none achieved insulin independence after AIT and required an average of 23.8 U of insulin/day. All 4 patients were narcotic dependent pre-operatively; 3 were analgesic free after surgery with 1 patient requiring 90 morphine equivalents/day. Preliminary results are inconclusive with regard to pain and metabolic outcomes, but show consistency in the up- and down- regulation of certain pancreatic genes irrespective of etiology.
Gene Expression