Journal
EBIOMEDICINE
Volume 50, Issue -, Pages 191-202Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2019.11.009
Keywords
High-grade serous ovarian cancer; HGSOC; Proteogenomic; ADNP; Poor prognostic marker
Funding
- National Cancer Institute of the National Institutes of Health [R00-CA166228]
- V Foundation for Cancer Research [V2016-013]
- New Jersey Commission for Cancer Research [DHFS-18PPC-024]
- [P30-CA072720-5921]
Ask authors/readers for more resources
Background: Despite toxic side effects and limited durable response, the current standard-of-care treatment for high grade serous ovarian cancer (HGSOC) remains platinum/taxane-based chemotherapy. Given that the overall prognosis has not improved drastically over the past several decades, there is a critical need to understand the underlying mechanisms that lead to tumour development and progression. Methods: We utilized an integrative proteogenomic analysis of HGSOC tumours applying a poor prognosis gene expression signature (PPS) as a conceptual framework to analyse orthogonal genomic and proteomic data from the TCGA (n = 488) and CPTAC (n=169) studies. Genes identified through in silico analyses were assessed in vitro studies to demonstrate their impact on proliferation and cell cycle progression. Findings: These analyses identified DNA amplification and overexpression of the transcription factor ADNP (Activity Dependent Neuroprotector Homeobox) in poorly prognostic tumours. Validation studies confirmed the prognostic capacity of ADNP and suggested an oncogenic role for this protein given the association between ADNP expression and pro-proliferative signalling. In vitro studies confirmed ADNP as a novel and essential mediator of cell proliferation through dysregulation of cell cycle checkpoints. Interpretation: We identified ADNP as being amplified and overexpressed in poor prognosis HGSOC in silico analyses and demonstrated that ADNP is a novel and essential oncogene in HGSOC which mediates proliferation through dysregulation of cell cycle checkpoints in vitro. (C) 2019 The Author(s). Published by Elsevier B.V.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available