Distinct molecular pathways in ovarian endometrioid adenocarcinoma with concurrent endometriosis

Chi Zhang, Xiyin Wang, Yanett Anaya, Luca Parodi, Lijun Cheng, Matthew L. Anderson, Shannon M. Hawkins

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Women with endometriosis, a benign growth of endometrial tissue outside the uterine cavity, are at increased risk of specific histotypes of epithelial ovarian cancer, such as ovarian endometrioid adenocarcinoma (OEA). Women with OEA who have endometriosis at time of surgical staging demonstrate improved clinical prognosis compared to women with OEA without evidence of endometriosis. However, the molecular contributions of the endometriotic tumor microenvironment to these ovarian cancers remain poorly understood. As a starting point, we used a platform for genome-wide transcriptomic profiling to compare specimens of OEA from women with and without concurrent endometriosis and benign reproductive tract tissues, including proliferative endometrium and typical and atypical endometrioma samples (n = 20). Principle component analysis revealed distinct clustering between benign and malignant samples as well as malignant samples with and without concurrent endometriosis. Examination of gene signatures revealed that OEA with concurrent endometriosis contained a unique molecular signature compared to OEA without concurrent endometriosis, distinguished by 682 unique genes differentially expressed (fold change < or >1.5, p < 0.01). Bioinformatic analysis of these differentially expressed gene products using ingenuity pathway analysis revealed activation of NFkB signaling, an inflammatory signaling pathway constitutively active in endometriosis. DAVID functional annotation clustering further revealed enrichment in RAS signaling as both cytoskeleton organization and GTPase regulator activity relied heavily on RAS protein signal transduction. Gene set enrichment analysis highlighted immune and inflammatory nodes involved in OEA with concurrent endometriosis. These observations provide novel resources for understanding molecular subtleties potentially involved in OEA within the context of the endometriotic tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)2505-2515
Number of pages11
JournalInternational Journal of Cancer
Volume143
Issue number10
DOIs
StatePublished - Nov 15 2018

Keywords

  • endometriosis
  • molecular pathways
  • ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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