4.5 Article

Epigenetic identification of ADCY4 as a biomarker for breast cancer: an integrated analysis of adenylate cyclases

Journal

EPIGENOMICS
Volume 11, Issue 14, Pages 1561-1579

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/epi-2019-0207

Keywords

adenylyl cyclases; biomarker; breast cancer; cAMP signaling pathway; DNA methylation; G protein-coupled receptor; lysophosphatidic acid receptor; prognosis

Funding

  1. Research Foundation of Southwest Medical University for Youth [090300030685]
  2. National Natural Science Foundation of China [81201682]
  3. Funded Project of Affiliated Hospital of Southwest Medical University for Doctors [17135]

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Aim: To explore the role of adenylyl cyclase isoforms and its epigenetics in cancer. Materials & methods: Adenylyl cyclase expression profiles, epigenetic alterations, prognostic value and molecular networks were assessed by use of public omics datasets. Results: ADCY4 was significantly downregulated in breast cancer. This downregulation was associated with promoter hypermethylation. High ADCY4 expression was correlated with better survival of patients with breast cancer and its different intrinsic subtypes and tumor stages. ADCY4 was shown to be strongly associated with G protein coupled receptors and the downstream cAMP signaling pathway, which was also significantly enriched in newly identified lysophosphatidic acid receptor 4 and glucagon-like peptide-1. Conclusion: ADCY4 may be used as an epigenetic biomarker for breast cancer, as well as a possible target for therapy.

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