In:
Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2010-12)
Abstract:
DNA polymerase η (pol η) is capable of bypassing DNA adducts produced by cisplatin or oxaliplatin and is associated with cellular tolerance to platinum. Previous studies showed that defective pol η resulted in enhanced cisplatin or oxaliplatin sensitivity in some cell lines. The purpose of the present study was to investigate the role of pol η protein expression in metastatic gastric adenocarcinoma. Methods Four gastric adenocarcinoma cell lines were chosen to explore the relationship between pol η protein expression and oxaliplatin sensitivity by western blotting and MTT assay. Eighty metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX regimen as first-line chemotherapy were analyzed, corresponding pretreatment formalin-fixed paraffin-embedded tumor tissues were used to detect pol η protein expression by immunohistochemistry. Relationship between pol η protein expression and clinical features and outcome of these patients was analyzed. Results A positive linear relationship between pol η protein expression and 48 h IC50 values of oxaliplatin in four gastric cancer cell lines was observed. Positivity of pol η protein expression was strongly associated with poor treatment response, as well as shorter survival at both univariate (8 versus 14 months; P 〈 0.001) and multivariate (hazard ratio, 4.555; 95% confidence interval, 2.461-8.429; P 〈 0.001) analysis in eighty metastatic gastric adenocarcinoma patients. Conclusions Our study indicates that polη is a predictive factor of treatment response and survival of metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX as first-line chemotherapy. Therefore confirming the value of polη in studies with prospective design is mandatory.
Type of Medium:
Online Resource
ISSN:
1479-5876
DOI:
10.1186/1479-5876-8-126
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2010
detail.hit.zdb_id:
2118570-0
