ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer

Shoko Mase, Keiko Shinjo, Haruhito Totani, Keisuke Katsushima, Atsushi Arakawa, Satoru Takahashi, Hung Cheng Lai, Ru Inn Lin, Michael W.Y. Chan, Mayumi Sugiura-Ogasawara, Yutaka Kondo

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum-based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome-wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P <.05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P =.049 and P =.021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum-based adjuvant chemotherapy.
原文英語
頁(從 - 到)1105-1116
頁數12
期刊Cancer Science
110
發行號3
DOIs
出版狀態已發佈 - 三月 1 2019

指紋

DNA Methylation
Ovarian Neoplasms
Recurrence
Platinum
Atlases
Biomarkers
Genome
Neoplasms
Adjuvant Chemotherapy
Methylation
Multivariate Analysis
Phenotype
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Mase, S., Shinjo, K., Totani, H., Katsushima, K., Arakawa, A., Takahashi, S., ... Kondo, Y. (2019). ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer. Cancer Science, 110(3), 1105-1116. https://doi.org/10.1111/cas.13936

ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer. / Mase, Shoko; Shinjo, Keiko; Totani, Haruhito; Katsushima, Keisuke; Arakawa, Atsushi; Takahashi, Satoru; Lai, Hung Cheng; Lin, Ru Inn; Chan, Michael W.Y.; Sugiura-Ogasawara, Mayumi; Kondo, Yutaka.

於: Cancer Science, 卷 110, 編號 3, 01.03.2019, p. 1105-1116.

研究成果: 雜誌貢獻文章

Mase, S, Shinjo, K, Totani, H, Katsushima, K, Arakawa, A, Takahashi, S, Lai, HC, Lin, RI, Chan, MWY, Sugiura-Ogasawara, M & Kondo, Y 2019, 'ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer', Cancer Science, 卷 110, 編號 3, 頁 1105-1116. https://doi.org/10.1111/cas.13936
Mase S, Shinjo K, Totani H, Katsushima K, Arakawa A, Takahashi S 等. ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer. Cancer Science. 2019 3月 1;110(3):1105-1116. https://doi.org/10.1111/cas.13936
Mase, Shoko ; Shinjo, Keiko ; Totani, Haruhito ; Katsushima, Keisuke ; Arakawa, Atsushi ; Takahashi, Satoru ; Lai, Hung Cheng ; Lin, Ru Inn ; Chan, Michael W.Y. ; Sugiura-Ogasawara, Mayumi ; Kondo, Yutaka. / ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer. 於: Cancer Science. 2019 ; 卷 110, 編號 3. 頁 1105-1116.
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abstract = "Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum-based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome-wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P <.05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P =.049 and P =.021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum-based adjuvant chemotherapy.",
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AU - Mase, Shoko

AU - Shinjo, Keiko

AU - Totani, Haruhito

AU - Katsushima, Keisuke

AU - Arakawa, Atsushi

AU - Takahashi, Satoru

AU - Lai, Hung Cheng

AU - Lin, Ru Inn

AU - Chan, Michael W.Y.

AU - Sugiura-Ogasawara, Mayumi

AU - Kondo, Yutaka

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N2 - Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum-based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome-wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P <.05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P =.049 and P =.021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum-based adjuvant chemotherapy.

AB - Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum-based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome-wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence ≤12 months, n = 51) and late recurrence serous ovarian cancer (LRS, recurrence >12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P <.05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P =.049 and P =.021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum-based adjuvant chemotherapy.

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