Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients.
Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients.
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DOI：
10.1186/s12885-015-1703-1
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发表时间：
2015-10-19
期刊：
影响因子：
3.8
通讯作者：
Konishi I
中科院分区：
文献类型：
--
作者：
Horikawa N;Baba T;Matsumura N;Murakami R;Abiko K;Hamanishi J;Yamaguchi K;Koshiyama M;Yoshioka Y;Konishi I
新辅助化疗（NAC）使用铂和伊立替康（CPT-11），然后根治性切除已被证明是局部晚期鳞状宫颈癌（SCC）患者的有效治疗方法。然而，在耐药或nac毒性病例中，手术治疗或放疗可能会延迟，并可能对预后产生不利影响。因此，建立一种预测NAC疗效的方法具有重要的意义。研究SCC组织样本（n = 12）的基因表达微阵列和血液样本（n = 23）的UGT1A1基因分型与NAC敏感性的关系。分析SCC细胞株的基因表达和药物敏感性。微阵列分析显示，nac耐药患者谷胱甘肽代谢途径（GMP）显著上调（p < 0.01）， 50%生长抑制浓度CPT-11与SCC细胞GMP激活预测评分呈正相关（r = 0.32, p < 0.05）。4种SCC细胞系细胞内谷胱甘肽（GSH）浓度与GMP评分呈高度正相关（r = 0.72）。UGT1A1基因分型显示，UGT1A1多态性患者对NAC的应答率显著高于野生型患者（分别为79.5%对49.5%,p < 0.05）。这些结果表明，癌组织的GMP评分结合血液样本的UGT1A1基因分型可以作为预测NAC对个体SCC患者疗效的高效标志物。本文的在线版本（doi:10.1186/s12885-015-1703-1）包含补充材料，仅供授权用户使用。
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. 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. Gene 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. Microarray 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). These 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. The online version of this article (doi:10.1186/s12885-015-1703-1) contains supplementary material, which is available to authorized users.