In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 24 ( 2015-12-15), p. 5612-5618
Abstract:
Purpose: GSK3β is a protein kinase that can suppress a number of key oncoproteins. We have previously shown in preclinical models of pancreatic ductal adenocarcinoma (PDAC) that inhibition of GSK3β causes stabilization and nuclear translocation of β-catenin, poor differentiation, proliferation, and resistance to radiation. The objective of this study was to determine its utility as a biomarker of clinical outcomes. Experimental Design: Automated Quantitative Immunofluorescence Analysis (AQUA) of GSK3β was performed on a tissue microarray with samples from 163 patients treated on RTOG 9704. On the basis of findings in an exploratory cohort, GSK3β was analyzed as a categorical variable using its upper quartile ( & gt;Q3) as a cut point. Overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan–Meier method, and GSK3β groupings were compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to determine associations between GSK3β and OS/DFS. Results: The 3-year OS rates for GSK3β≤Q3 versus GSK3β & gt;Q3 were 16% (95% confidence intervals; CI, 10%–23%) and 30% (95% CI, 17%–44%), respectively, P = 0.0082. The 3-year DFS rates were 9% (95% CI, 5%–15%) and 20% (95% CI, 9%–33%) respectively, P value = 0.0081. On multivariable analysis, GSK3β was a significant predictor of OS. Patients with GSK3β & gt;Q3 had a 46% reduced risk of dying of pancreatic cancer (HR, 0.54; 95% CI, 0.31–0.96, P value = 0.034). The HR for DFS was 0.65 (95% CI, 0.39–1.07; P value = 0.092). Conclusions: GSK3β expression is a strong prognosticator in PDAC, independent of other known factors such as tumor (T) stage, nodal status, surgical margins and CA19-9. Clin Cancer Res; 21(24); 5612–8. ©2015 AACR.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-15-0789
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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