Journal of Gastrointestinal & Digestive System
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Dysregulation of KRAS signaling in pancreatic cancer is not associated with KRAS mutations and outcome
Co-Organized Event 13th International Conference on Clinical Gastroenterology & Hepatology & 2nd International Conference on Digestive Diseases
Oliverius M, Brynychova V, Hughes D J, Hlavac V, Dvorak P, Doherty J E, Murray H A and Lemstrova R
Institute of Clinical and Experimental Medicine, Czech National Institute of Public Health, Czech Royal College of Surgeons in Ireland, Ireland Charles University in Prague, Czech Randox Laboratories Ltd, Crumlin, UK Palacky University Olomouc and University Hospital Olomouc, Czech
Posters & Accepted Abstracts: J Gastrointest Dig Syst
DOI:
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is known as cancer with very poor prognosis. KRAS oncogene is a major driver of PDAC tumorigenesis but its role as prognostic or predictive factor is not clear. The aim of the present study was to investigate the prognostic significance of KRAS downstream signaling pathway genes expression and association with clinical characteristics in PDAC patients undergoing radical surgery. Methods: Tumors and adjacent non-neoplastic pancreatic tissues were examined in 45 patients with histologically verified PDAC. KRAS, BRAF and PIK3CA gene mutation analysis was performed using the KRAS/BRAF/PIK3CA array. The transcript profile of 52 KRAS downstream signaling pathway genes was assessed using quantitative real-time polymerase chain reaction. Results: KRAS mutation was detected in 80% of cases but the mutation status do not influence PDAC patient芒�?�?s prognoses. The genes of four signaling pathways downstream of KRAS including the PI3K/PDK1/AKT, RAL guanine nucleotide exchange factor, RIN1/ABL, and RAF/MAPK pathways exhibited differential expression in PDAC compared to the adjacent normal tissue. However, no significant differences in expression were evident between patients with KRAS mutated and wild type tumors. Moreover, expression patterns of KRAS downstream signaling pathway do not associate with overall survival of patients. Conclusions: KRAS mutation is present in most cases of PDAC, but is not associated with changes in expression of KRAS downstream signaling pathways and clinical outcome.Biography
Martin Oliverius is Deputy Head of Transplant Surgery Department and Director of small bowel transplantation program at Institute for Clinical and Experimental Medicine, Pargue, Czech Republic.
