Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target

Chin Sheng Hung, Sheng Chao Wang, Yi Ting Yen, Tzong Huei Lee, Wu Che Wen, Ruo Kai Lin

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22 引文 斯高帕斯(Scopus)


Lung and breast cancer are the leading causes of mortality in women worldwide. The discovery of molecular alterations that underlie these two cancers and corresponding drugs has contributed to precision medicine. We found that CCND2 is a common target in lung and breast cancer. Hypermethylation of the CCND2 gene was reported previously; however, no comprehensive study has investigated the clinical significance of CCND2 alterations and its applications and drug discovery. Genome-wide methylation and quantitative methylation-specific real-time polymerase chain reaction (PCR) showed CCND2 promoter hypermethylation in Taiwanese breast cancer patients. As compared with paired normal tissues and healthy individuals, CCND2 promoter hypermethylation was detected in 40.9% of breast tumors and 44.4% of plasma circulating cell-free DNA of patients. The western cohort of The Cancer Genome Atlas also demonstrated CCND2 promoter hypermethylation in female lung cancer, lung adenocarcinoma, and breast cancer patients and that CCND2 promoter hypermethylation is an independent poor prognostic factor. The cell model assay indicated that CCND2 expression inhibited cancer cell growth and migration ability. The demethylating agent antroquinonol D upregulated CCND2 expression, caused cell cycle arrest, and inhibited cancer cell growth and migration ability. In conclusion, hypermethylation of CCND2 is a potential diagnostic, prognostic marker and drug target, and it is induced by antroquinonol D.
期刊International Journal of Molecular Sciences
出版狀態已發佈 - 十月 10 2018


  • Antrodia camphorata
  • antroquinonol D
  • CCND2
  • circulating cell-free DNA
  • hypermethylation
  • lung adenocarcinoma
  • prognostic factor
  • triple-negative breast cancer (TNBC)
  • tumor suppressor gene

ASJC Scopus subject areas

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學


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