Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients

BMC Cancer

Research Article

Ken Yamaguchi¹  Naoki Horikawa¹  Masafumi Koshiyama¹  Yumiko Yoshioka¹  Tsukasa Baba¹  Noriomi Matsumura¹  Kaoru Abiko¹  Ryusuke Murakami¹  Ikuo Konishi¹  Junzo Hamanishi¹ 

[1] Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, 606-8507, Kyoto, Sakyo-ku, Japan;

关键词: Neoadjuvant chemotherapy;    Cervical cancer;    Bioinformatics;    Glutathione pathway;    UGT1A1;   

DOI  :  10.1186/s12885-015-1703-1

 received in 2015-01-29, accepted in 2015-10-07,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Horikawa et al. 2015