Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer

R Qin; T C Smyrk; N R Reed; R L Schmidt; T Schnelldorfer; S T Chari; G M Petersen; A H Tang

doi:10.1038/bjc.2014.659

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Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer

Journal article

Open access

Peer reviewed

Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer

R Qin, T C Smyrk, N R Reed, R L Schmidt, T Schnelldorfer, S T Chari, G M Petersen and A H Tang

British journal of cancer, Vol.112(3), pp.514-522

02/03/2015

DOI: 10.1038/bjc.2014.659

PMCID: PMC4453663

PMID: 25584484

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https://doi.org/10.1038/bjc.2014.659View

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Abstract

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. 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. 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. 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.

Aged

Biomarkers, Tumor - analysis

Biomarkers, Tumor - metabolism

Carcinoma, Pancreatic Ductal - mortality

Carcinoma, Pancreatic Ductal - pathology

Carcinoma, Pancreatic Ductal - surgery

Cell Proliferation

Female

Humans

Hypoxia-Inducible Factor 1, alpha Subunit - analysis

Hypoxia-Inducible Factor 1, alpha Subunit - metabolism

Ki-67 Antigen - analysis

Ki-67 Antigen - metabolism

Male

Middle Aged

Pancreatic Neoplasms - mortality

Pancreatic Neoplasms - pathology

Pancreatic Neoplasms - surgery

Prognosis

Proto-Oncogene Proteins - analysis

Proto-Oncogene Proteins - metabolism

Proto-Oncogene Proteins p21(ras)

ras Proteins - analysis

ras Proteins - metabolism

Signal Transduction

Survival Analysis

Tissue Array Analysis

Details

Title: Subtitle: Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer
Creators: R Qin - Mayo Clinic
T C Smyrk - Mayo Clinic in Arizona
N R Reed - Mayo Clinic in Arizona
R L Schmidt - Mayo Clinic in Arizona
T Schnelldorfer - Mayo Clinic in Arizona
S T Chari - Mayo Clinic in Arizona
G M Petersen - Mayo Clinic
A H Tang - Mayo Clinic in Arizona
Resource Type: Journal article
Publication Details: British journal of cancer, Vol.112(3), pp.514-522
DOI: 10.1038/bjc.2014.659
PMID: 25584484
PMCID: PMC4453663
ISSN: 0007-0920
eISSN: 1532-1827
Grant note: CA140550 / NCI NIH HHS R01 GM069922 / NIGMS NIH HHS R01 CA140550 / NCI NIH HHS GM069922-06S1 / NIGMS NIH HHS P30 CA015083 / NCI NIH HHS P50 CA102701 / NCI NIH HHS
Language: English
Date published: 02/03/2015
Academic Unit: Surgery
Record Identifier: 9984701651902771

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