Use of DNA polymerase η protein expression to predict treatment response and survival of metastatic gastric adenocarcinoma patients treated with oxaliplatin-based chemotherapy.

Abstract

e14632 Background: DNA polymerase η (pol η) is capable of bypassing DNA adducts caused by cisplatin or oxaliplatin and is associated with cellular tolerance to platinums. 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 chosed to explore the relationship between pol η protein expression level 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 collected, 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 analysis. Results: A positive linear relationship between pol η protein expression level and 48h IC50 values of oxaliplatin in four gastric cancer cell lines was observed. Positivity of pol η protein expression were strongly associated with poor treatment response, and also shorter survival at both univariate (8 versus 14 months; p < 0.001) and multivariate (hazard ratio, 3.932; 95% confidence interval, 2.278-6.785; p < 0.001) in eighty metastatic gastric adenocarcinoma. Conclusions: Above data indicates pol η is a treatment-response predictive marker of treatment response and survival of metastatic gastric adenocarcinoma patients treated with first-line FOLFOX or XELOX chemotherapy and it is worthy of further randomed controlled clinical trials to confirm. No significant financial relationships to disclose.