Abstract
BackgroundNeoadjuvant chemotherapy (NAC) using platinum and irinotecan (CPT-11) followed by radical excision has been shown to be a valid treatment for locally advanced squamous cervical cancer (SCC) patients. However, in NAC-resistant or NAC-toxic cases, surgical treatment or radiotherapy might be delayed and the prognosis may be adversely affected. Therefore, it is important to establish a method to predict the efficacy of NAC.MethodsGene expression microarrays of SCC tissue samples (n = 12) and UGT1A1 genotyping of blood samples (n = 23) were investigated in terms of their association with NAC sensitivity. Gene expression and drug sensitivity of SCC cell lines were analyzed for validation.ResultsMicroarray analysis revealed that the glutathione metabolic pathway (GMP) was significantly up-regulated in NAC-resistant patients (p < 0.01), and there was a positive correlation between 50 % growth inhibitory concentrations of CPT-11 and predictive scores of GMP activation in SCC cells (r = 0.32, p < 0.05). The intracellular glutathione (GSH) concentration showed a highly positive correlation with GMP scores among 4 SCC cell lines (r = 0.72). UGT1A1 genotyping revealed that patients with UGT1A1 polymorphisms exhibited significantly higher response rates to NAC than those with the wild-type (79.5 vs. 49.5 %, respectively, p < 0.05).ConclusionsThese results indicate that GMP scores of cancerous tissue combined with UGT1A1 genotyping of blood samples may serve as highly potent markers for predicting the efficacy of NAC for individual SCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1703-1) contains supplementary material, which is available to authorized users.
Highlights
Neoadjuvant chemotherapy (NAC) using platinum and irinotecan (CPT-11) followed by radical excision has been shown to be a valid treatment for locally advanced squamous cervical cancer (SCC) patients
It is well-known that irinotecan (CPT-11) causes severe side effects more frequently in patients with UDP glucuronosyltransferase 1 family (UGT1A1) polymorphisms than the wild-type [9], and, UGT1A1 genotyping is a prerequisite before initiating chemotherapy using CPT-11 in a clinical setting
We assessed whether the chemo-susceptibility of locally advanced cervical cancer (LACC) could be evaluated based on tumor expression microarray analysis and host UGT1A1 genotyping, in order to optimize the efficacy of NAC-radical hysterectomy (RH)
Summary
Neoadjuvant chemotherapy (NAC) using platinum and irinotecan (CPT-11) followed by radical excision has been shown to be a valid treatment for locally advanced squamous cervical cancer (SCC) patients. It is well-known that irinotecan (CPT-11) causes severe side effects more frequently in patients with UGT1A1 polymorphisms than the wild-type [9], and, UGT1A1 genotyping is a prerequisite before initiating chemotherapy using CPT-11 in a clinical setting It remains unclear whether CPT-11 treatment is more effective in LACC patients with UGT1A1 polymorphisms. We assessed whether the chemo-susceptibility of LACC could be evaluated based on tumor expression microarray analysis and host UGT1A1 genotyping, in order to optimize the efficacy of NAC-RH
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