Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biomolecules, Vol 12, Iss 10, p 1379 (2022)
Druh dokumentu: article
ISSN: 2218-273X
DOI: 10.3390/biom12101379
Popis: The aim of the present study was to determine which individual or combined CpG sites among O6-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.
Databáze: Directory of Open Access Journals
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