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タイトル: | Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients |
著者: | Horikawa, Naoki Baba, Tsukasa Matsumura, Noriomi Murakami, Ryusuke Abiko, Kaoru Hamanishi, Junzo https://orcid.org/0000-0002-7750-0623 (unconfirmed) Yamaguchi, Ken Koshiyama, Masafumi Yoshioka, Yumiko Konishi, Ikuo |
著者名の別形: | 馬場, 長 松村, 謙臣 村上, 隆介 安彦, 郁 濵西, 潤三 山口, 建 越山, 雅文 吉岡, 弓子 小西, 郁生 |
キーワード: | Neoadjuvant chemotherapy Cervical cancer Bioinformatics Glutathione pathway UGT1A1 polymorphism |
発行日: | 19-Oct-2015 |
出版者: | BioMed Central Ltd. |
誌名: | BMC Cancer |
巻: | 15 |
論文番号: | 739 |
抄録: | Background: 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. Methods: 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. Results: 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). Conclusions: 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. |
著作権等: | © 2015 Horikawa et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
URI: | http://hdl.handle.net/2433/210415 |
DOI(出版社版): | 10.1186/s12885-015-1703-1 |
PubMed ID: | 26482555 |
出現コレクション: | 学術雑誌掲載論文等 |
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