One of the major challenges in pancreatic cancer research is the availability of clinical samples from patients undergoing surgical resection with complete demographic and clinico-pathological information. In our ongoing efforts, we have been successful in establishing multiple cohorts of resected pancreatic cancer samples from cases in the United States and abroad. This includes a new approved study protocol to collect tumors and/or blood samples from 500 PDAC cases in the greater Baltimore area with myself as principal investigator. This collection will be an invaluable asset for our pancreatic cancer program. The results from our pilot gene-expression profiling study showed that a lower expression of DPEP1 (dipeptidase 1) in tumors was associated with poorer survival in two independent cohorts of PDAC and was independent of stage and resection margin status (Zhang et. al., PLoS One, 2012). DPEP1 expression was significantly lower in tumors as compared to adjacent non-tumor pancreas from the same patient in both the cohorts. Overexpression of DPEP1 in pancreatic cancer cell lines inhibited cell migration and invasion, and increased the sensitivity to gemcitabine, a first-line drug for treating pancreatic cancer. We also showed that DPEP1 is regulated by EGF/MEK/MAPK pathway, and MEK1/2 inhibitor enhanced DPEP1 expression in vitro. In view of these findings, we propose that re-expression of DPEP1 by novel approaches could be useful for the treatment of PDAC in improving patient survival. Currently, we are testing the hypothesis that DPEP1 inhibits tumor progression in vivo. In our continuing effort of examining the tumor biology associated with disease aggressiveness, we are currently comparing the gene expression profile of tumors in two groups of resected patients: one with a short survival (<7 months) and the other with a longer survival (24-70 months) following resection, and further testing the hypotheses that a) Inflammatory genes drive tumor aggressiveness in resected patients and b) Inflammation-associated gene signature defines aggressive subtypes in resectable PDAC.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Cancer Institute Division of Basic Sciences
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Wang, Jian; Hussain, S Perwez (2017) NO(•) and Pancreatic Cancer: A Complex Interaction with Therapeutic Potential. Antioxid Redox Signal 26:1000-1008
Wang, Jian; Yang, Shouhui; He, Peijun et al. (2016) Endothelial Nitric Oxide Synthase Traffic Inducer (NOSTRIN) is a Negative Regulator of Disease Aggressiveness in Pancreatic Cancer. Clin Cancer Res 22:5992-6001
Hussain, S Perwez (2016) Pancreatic Cancer: Current Progress and Future Challenges. Int J Biol Sci 12:270-2
Budhu, Anuradha; Terunuma, Atsushi; Zhang, Geng et al. (2014) Metabolic profiles are principally different between cancers of the liver, pancreas and breast. Int J Biol Sci 10:966-72
Zhang, Geng; He, Peijun; Gaedcke, Jochen et al. (2013) FOXL1, a novel candidate tumor suppressor, inhibits tumor aggressiveness and predicts outcome in human pancreatic cancer. Cancer Res 73:5416-25
Zhang, Geng; He, Peijun; Tan, Hanson et al. (2013) Integration of metabolomics and transcriptomics revealed a fatty acid network exerting growth inhibitory effects in human pancreatic cancer. Clin Cancer Res 19:4983-93
Zhang, Geng; Schetter, Aaron; He, Peijun et al. (2012) DPEP1 inhibits tumor cell invasiveness, enhances chemosensitivity and predicts clinical outcome in pancreatic ductal adenocarcinoma. PLoS One 7:e31507