Background:In search of potential biomarkers of drug responsiveness the tumour suppressor PLK2 has been identified as a mediator of taxane sensitivity in some tumour types,based on its role of G2M checkpoint regulatio...Background:In search of potential biomarkers of drug responsiveness the tumour suppressor PLK2 has been identified as a mediator of taxane sensitivity in some tumour types,based on its role of G2M checkpoint regulation.Objective:The current study set out to evaluate PLK2 methylation in breast cancer treated with neo-adjuvant chemotherapy including a taxane,as a biomarker of disease progression.Methods:Silencing of PLK2 in MCF-7 cells followed by taxane treatment was assessed using apoptotic readout for proof of principle.DNA was extracted from 64 cases of diagnostic surgical FFPE sections.Using pyrosequencing,levels of PLK2 promoter methylation were measured.Results:Silencing of PLK2 resulted in a significantly reduced apoptotic response following paclitaxel treatment(compared with scramble transfected controls).An association with higher levels of CpG island promoter methylation was seen for those cases with a progression-free survival(PFS)of less than 12 months.Kaplan-Meier analysis showed there was an association between overall survival(OS)and level of methylation(p=.06).Conclusions:Thus,based on data obtained from this pilot study,further larger studies evaluating the utility of PLK2 methylation as a potential predictive biomarker in breast cancer are warranted.展开更多
基金funding from Breast Cancer Campaign UK for a grant to support this work(HMC).
文摘Background:In search of potential biomarkers of drug responsiveness the tumour suppressor PLK2 has been identified as a mediator of taxane sensitivity in some tumour types,based on its role of G2M checkpoint regulation.Objective:The current study set out to evaluate PLK2 methylation in breast cancer treated with neo-adjuvant chemotherapy including a taxane,as a biomarker of disease progression.Methods:Silencing of PLK2 in MCF-7 cells followed by taxane treatment was assessed using apoptotic readout for proof of principle.DNA was extracted from 64 cases of diagnostic surgical FFPE sections.Using pyrosequencing,levels of PLK2 promoter methylation were measured.Results:Silencing of PLK2 resulted in a significantly reduced apoptotic response following paclitaxel treatment(compared with scramble transfected controls).An association with higher levels of CpG island promoter methylation was seen for those cases with a progression-free survival(PFS)of less than 12 months.Kaplan-Meier analysis showed there was an association between overall survival(OS)and level of methylation(p=.06).Conclusions:Thus,based on data obtained from this pilot study,further larger studies evaluating the utility of PLK2 methylation as a potential predictive biomarker in breast cancer are warranted.
