Article Abstract

GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients

Authors: Guochun Zhang, Xueke Qian, Chongyang Ren, Lingzhu Wen, Haitong Lyu, Ning Liao

Abstract

Background: Investigations of the 21-gene Oncotype DX assay in neoadjuvant settings for breast cancer patients are currently underdeveloped. It is still unclear whether any individual gene of the 16 cancer-related genes can be used to predict response to taxane-based neoadjuvant chemotherapy.
Methods: Here, we performed TaqMan RT-PCR reactions to profile the expression patterns of these genes in 66 Chinese ER-positive breast cancer patients’ tumor tissues who underwent taxane-based neoadjuvant chemotherapies. Only GSTM1 has distinct non-expression/expression polymorphism, and we observed an almost 2.5-fold increment in the possibility of achieving pathological complete response (pCR) was defined as no histological evidence of residual invasive cancer both in the breast and in the axilla. in GSTM1 non-expression patients. We then analyzed the expression levels of 4 main GST isozymes (GSTA1, GSTT1, GSTP1 and GSTT1) and docetaxel cytotoxicity in various breast cancer cell lines (MCF7, MDA-MB-231, BT474, and SKBR3). Furthermore, we knocked down 4 GST isozymes with siRNA against each isoform in resistant MDA-MB-231. We then observed the changes of docetaxel sensitivity though WST-1 assay, in addition to apoptosis by Hoechst stain and TUNEL assay.
Results: Docetaxel IC50 values ranging from 33.0 nM (MDA-MB-231) to 7.20 µM (resistant MDA-MB-231) revealed a close correlation with the expression levels of 4 main GST isozymes. Significantly, depletion of GSTM1 and GSTA1 but not GSTP1 nor GSTT1, suppressed cell viability by 174% and 155% respectively, and was able to induce obvious apoptosis in resistant MDA-MB-132.
Conclusions: Taken together, our results suggest that GSTM1 polymorphism could be useful in the prediction of taxane-based neoadjuvant chemotherapy in ER-positive Chinese breast cancer patients, and that GSTM1 and GSTA1 expression are linked to docetaxel resistance.