Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy
The aim of the present study was to determine which individual or combined CpG sites among O<sup>6</sup>-methylguanine DNA methyltransferase CpG 74–89 in glioblastoma mainly affects the response to temozolomide resulting from CpG methylation using statistical analyses focused on the tumo...
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MDPI AG
2022-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/10/1379 |
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| author | Tomohiro Hosoya Masamichi Takahashi Calvin Davey Jun Sese Mai Honda-Kitahara Yasuji Miyakita Makoto Ohno Shunsuke Yanagisawa Takaki Omura Daisuke Kawauchi Yukie Ozeki Miyu Kikuchi Tomoyuki Nakano Akihiko Yoshida Hiroshi Igaki Yuko Matsushita Koichi Ichimura Yoshitaka Narita |
| author_facet | Tomohiro Hosoya Masamichi Takahashi Calvin Davey Jun Sese Mai Honda-Kitahara Yasuji Miyakita Makoto Ohno Shunsuke Yanagisawa Takaki Omura Daisuke Kawauchi Yukie Ozeki Miyu Kikuchi Tomoyuki Nakano Akihiko Yoshida Hiroshi Igaki Yuko Matsushita Koichi Ichimura Yoshitaka Narita |
| author_sort | Tomohiro Hosoya |
| collection | DOAJ |
| description | The aim of the present study was to determine which individual or combined CpG sites among O<sup>6</sup>-methylguanine DNA methyltransferase CpG 74–89 in glioblastoma mainly affects the response to temozolomide resulting from CpG methylation using statistical analyses focused on the tumor volume ratio (TVR). We retrospectively examined 44 patients who had postoperative volumetrically measurable residual tumor tissue and received adjuvant temozolomide therapy for at least 6 months after initial chemoradiotherapy. TVR was defined as the tumor volume 6 months after the initial chemoradiotherapy divided by that before the start of chemoradiotherapy. Predictive values for TVR as a response to adjuvant therapy were compared among the averaged methylation percentages of individual or combined CpGs using the receiver operating characteristic curve. Our data revealed that combined CpG 78 and 79 showed a high area under the curve (AUC) and a positive likelihood ratio and that combined CpG 76–79 showed the highest AUC among all combinations. AUCs of consecutive CpG combinations tended to be higher for CpG 74–82 in exon 1 than for CpG 83–89 in intron 1. In conclusion, the methylation status at CpG sites in exon 1 was strongly associated with TVR reduction in glioblastoma. |
| first_indexed | 2024-03-09T20:37:15Z |
| format | Article |
| id | doaj.art-b3d3b004e156448c896aaac5b70f88ae |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:37:15Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b3d3b004e156448c896aaac5b70f88ae2023-11-23T23:07:42ZengMDPI AGBiomolecules2218-273X2022-09-011210137910.3390/biom12101379Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide EfficacyTomohiro Hosoya0Masamichi Takahashi1Calvin Davey2Jun Sese3Mai Honda-Kitahara4Yasuji Miyakita5Makoto Ohno6Shunsuke Yanagisawa7Takaki Omura8Daisuke Kawauchi9Yukie Ozeki10Miyu Kikuchi11Tomoyuki Nakano12Akihiko Yoshida13Hiroshi Igaki14Yuko Matsushita15Koichi Ichimura16Yoshitaka Narita17Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanHumanome Laboratory, 2-4-10 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanHumanome Laboratory, 2-4-10 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanDepartment of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanThe aim of the present study was to determine which individual or combined CpG sites among O<sup>6</sup>-methylguanine DNA methyltransferase CpG 74–89 in glioblastoma mainly affects the response to temozolomide resulting from CpG methylation using statistical analyses focused on the tumor volume ratio (TVR). We retrospectively examined 44 patients who had postoperative volumetrically measurable residual tumor tissue and received adjuvant temozolomide therapy for at least 6 months after initial chemoradiotherapy. TVR was defined as the tumor volume 6 months after the initial chemoradiotherapy divided by that before the start of chemoradiotherapy. Predictive values for TVR as a response to adjuvant therapy were compared among the averaged methylation percentages of individual or combined CpGs using the receiver operating characteristic curve. Our data revealed that combined CpG 78 and 79 showed a high area under the curve (AUC) and a positive likelihood ratio and that combined CpG 76–79 showed the highest AUC among all combinations. AUCs of consecutive CpG combinations tended to be higher for CpG 74–82 in exon 1 than for CpG 83–89 in intron 1. In conclusion, the methylation status at CpG sites in exon 1 was strongly associated with TVR reduction in glioblastoma.https://www.mdpi.com/2218-273X/12/10/1379glioblastomavolumetric analysispyrosequencingCpG site |
| spellingShingle | Tomohiro Hosoya Masamichi Takahashi Calvin Davey Jun Sese Mai Honda-Kitahara Yasuji Miyakita Makoto Ohno Shunsuke Yanagisawa Takaki Omura Daisuke Kawauchi Yukie Ozeki Miyu Kikuchi Tomoyuki Nakano Akihiko Yoshida Hiroshi Igaki Yuko Matsushita Koichi Ichimura Yoshitaka Narita Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy Biomolecules glioblastoma volumetric analysis pyrosequencing CpG site |
| title | Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy |
| title_full | Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy |
| title_fullStr | Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy |
| title_full_unstemmed | Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy |
| title_short | Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy |
| title_sort | volumetric analysis of glioblastoma for determining which cpg sites should be tested by pyrosequencing to predict temozolomide efficacy |
| topic | glioblastoma volumetric analysis pyrosequencing CpG site |
| url | https://www.mdpi.com/2218-273X/12/10/1379 |
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