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Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study.

Publication ,  Journal Article
Devor, EJ; Miecznikowski, J; Schickling, BM; Gonzalez-Bosquet, J; Lankes, HA; Thaker, P; Argenta, PA; Pearl, ML; Zweizig, SL; Mannel, RS ...
Published in: Gynecol Oncol
December 2017

OBJECTIVE: Endometrial cancer can be diagnosed early and cured, yet cases that recur portend a very poor prognosis with over 10,000 women succumbing to the disease every year. In this study we addressed the question of how to recognize cases likely to recur early in the course of therapy using dysregulation of tumor microRNAs (miRNAs) as predictors. METHODS: Using the tissue collection from Gynecologic Oncology Group Study-210, we selected and analyzed expression of miRNAs in 54 recurrent and non-recurrent cases. The three most common histologic types, endometrioid adenocarcinoma (EEA), serous adenocarcinoma (ESA) and carcinosarcoma (UCS), were analyzed as three independent sets and their miRNA expression profiles compared. RESULTS: Only one miRNA was statistically different between recurrent and non-recurrent cases, and in only one histologic type: significant down-regulation of miR-181c was observed in EEA recurrence. Using several well-known databases to assess miR-181c targets, one target of particular relevance to cancer, NOTCH2, was well supported. Using The Cancer Genome Atlas and our validation tumor panel from the GOG-210 cohort, we confirmed that NOTCH2 is significantly over-expressed in EEA. In the most relevant endometrial adenocarcinoma cell model, Ishikawa H, altering miR-181c expression produces significant changes in NOTCH2 expression, consistent with direct targeting. CONCLUSIONS: Our findings suggest that increased NOTCH2 via loss of miR-181c is a significant component of EEA recurrence. This presents an opportunity to develop miR-181c and NOTCH2 as markers for early identification of high risk cases and the use of NOTCH inhibitors in the prevention or treatment of recurrent disease.

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Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

December 2017

Volume

147

Issue

3

Start / End Page

648 / 653

Location

United States

Related Subject Headings

  • Receptor, Notch2
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • MicroRNAs
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • Endometrial Neoplasms
  • Carcinoma, Endometrioid
  • 3215 Reproductive medicine
 

Citation

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Devor, E. J., Miecznikowski, J., Schickling, B. M., Gonzalez-Bosquet, J., Lankes, H. A., Thaker, P., … Leslie, K. K. (2017). Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol, 147(3), 648–653. https://doi.org/10.1016/j.ygyno.2017.09.025
Devor, Eric J., Jeffrey Miecznikowski, Brandon M. Schickling, Jesus Gonzalez-Bosquet, Heather A. Lankes, Premal Thaker, Peter A. Argenta, et al. “Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study.Gynecol Oncol 147, no. 3 (December 2017): 648–53. https://doi.org/10.1016/j.ygyno.2017.09.025.
Devor EJ, Miecznikowski J, Schickling BM, Gonzalez-Bosquet J, Lankes HA, Thaker P, et al. Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017 Dec;147(3):648–53.
Devor, Eric J., et al. “Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study.Gynecol Oncol, vol. 147, no. 3, Dec. 2017, pp. 648–53. Pubmed, doi:10.1016/j.ygyno.2017.09.025.
Devor EJ, Miecznikowski J, Schickling BM, Gonzalez-Bosquet J, Lankes HA, Thaker P, Argenta PA, Pearl ML, Zweizig SL, Mannel RS, Brown A, Ramirez NC, Ioffe OB, Park KJ, Creasman WT, Birrer MJ, Mutch D, Leslie KK. Dysregulation of miR-181c expression influences recurrence of endometrial endometrioid adenocarcinoma by modulating NOTCH2 expression: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017 Dec;147(3):648–653.
Journal cover image

Published In

Gynecol Oncol

DOI

EISSN

1095-6859

Publication Date

December 2017

Volume

147

Issue

3

Start / End Page

648 / 653

Location

United States

Related Subject Headings

  • Receptor, Notch2
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • MicroRNAs
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • Endometrial Neoplasms
  • Carcinoma, Endometrioid
  • 3215 Reproductive medicine