TY - JOUR
T1 - Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer
AU - Qin, R.
AU - Smyrk, T. C.
AU - Reed, N. R.
AU - Schmidt, R. L.
AU - Schnelldorfer, T.
AU - Chari, S. T.
AU - Petersen, G. M.
AU - Tang, A. H.
N1 - Publisher Copyright:
© 2015 Cancer Research UK. All rights reserved 0007 - 0920/15.
PY - 2015/2/3
Y1 - 2015/2/3
N2 - Background:The dismal prognosis of patients diagnosed with pancreatic cancer points to our limited arsenal of effective anticancer therapies. Oncogenic K-RAS hyperactivation is virtually universal in pancreatic cancer, that confers drug resistance, drives aggressive tumorigenesis and rapid metastasis. Pancreatic tumours are often marked by hypovascularity, increased hypoxia and ineffective drug delivery. Thus, biomarker discovery and developing innovative means of countervailing oncogenic K-RAS activation are urgently needed.Methods:Tumour specimens from 147 pancreatic cancer patients were analysed by immunohistochemical (IHC) staining and tissue microarray (TMA). Statistical correlations between selected biomarkers and clinicopathological predictors were examined to predict survival.Results:We find that heightened hypoxia response predicts poor clinical outcome in resectable pancreatic cancer. SIAH is a tumour-specific biomarker. The combination of five biomarkers (EGFR, phospho-ERK, SIAH, Ki67 and HIF-1α) and four clinicopathological predictors (tumour size, pathological grade, margin and lymph node status) predict patient survival post surgery in pancreatic cancer.Conclusions:Combining five biomarkers in the K-RAS/Ki67/HIF-1α pathways with four clinicopathological predictors may assist to better predict survival in resectable pancreatic cancer.
AB - Background:The dismal prognosis of patients diagnosed with pancreatic cancer points to our limited arsenal of effective anticancer therapies. Oncogenic K-RAS hyperactivation is virtually universal in pancreatic cancer, that confers drug resistance, drives aggressive tumorigenesis and rapid metastasis. Pancreatic tumours are often marked by hypovascularity, increased hypoxia and ineffective drug delivery. Thus, biomarker discovery and developing innovative means of countervailing oncogenic K-RAS activation are urgently needed.Methods:Tumour specimens from 147 pancreatic cancer patients were analysed by immunohistochemical (IHC) staining and tissue microarray (TMA). Statistical correlations between selected biomarkers and clinicopathological predictors were examined to predict survival.Results:We find that heightened hypoxia response predicts poor clinical outcome in resectable pancreatic cancer. SIAH is a tumour-specific biomarker. The combination of five biomarkers (EGFR, phospho-ERK, SIAH, Ki67 and HIF-1α) and four clinicopathological predictors (tumour size, pathological grade, margin and lymph node status) predict patient survival post surgery in pancreatic cancer.Conclusions:Combining five biomarkers in the K-RAS/Ki67/HIF-1α pathways with four clinicopathological predictors may assist to better predict survival in resectable pancreatic cancer.
KW - clinicopathological predictors
KW - hypoxia
KW - oncogenic K-RAS signalling pathway
KW - pancreatic cancer
KW - prognostic biomarkers
UR - http://www.scopus.com/inward/record.url?scp=84964284177&partnerID=8YFLogxK
U2 - 10.1038/bjc.2014.659
DO - 10.1038/bjc.2014.659
M3 - Article
C2 - 25584484
AN - SCOPUS:84964284177
SN - 0007-0920
VL - 112
SP - 514
EP - 522
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -