Role of Inflammation in the Development and Progression of Pancreatic Cancer

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In our initial approach, the expression of 25 inflammatory genes and 9 miRNAs were analyzed by quantitative RT/PCR in snap-frozen pancreatic ductal adenocarcinoma (PDAC) samples from 27 cases. In 18 of these cases surrounding non-tumorous pancreas from the same patients were also examined. The selected 25 inflammatory gene expression were earlier investigated in our laboratory to determine their prognostic significance in colon cancer. The selection of 9 miRNA was based on their differential expression in pancreatic cancer as reported earlier. Our preliminary data shows that an increased expression of macrophage migration inhibitory factor (MIF), IL-23, Annexin A1 and miR-210 is associated with poorer prognosis. We are currently validating these results in an independent cohort of PDAC. In our investigation of the role of FOX transcription factors in pancreatic cancer, we have preliminary data showing a lower expression of FOXA3 in tumors as compared to non-tumor tissue in the patients with PDAC. This observation was further validated in an independent cohort of PDAC cases. Currently, we are investigating the potential role of FOXA3 in the development and progression of pancreatic cancer by applying over- expression and knock-down strategy in pancreatic cancer cell lines. Our investigations also found that a lower expression of FOXL1 is associated with poorer survival in PDAC cases. We are currently validating this finding in an independent cohort of PDAC cases. Lastly, we found that a significantly higher number of cells expressed cytoplasmic phosphorylated-FOXO3 in tumors as compared to the surrounding nontumor tissue in PDAC cases as determined by immunohistochemical staining. This observation is being validated in an independent cohort of PDAC cases.