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Open Access 01-12-2019 | Ovarian Cancer | Research

Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer

Authors: Elizabeth V. Connor, Caner Saygin, Chad Braley, Andrew C. Wiechert, Sheelarani Karunanithi, Katie Crean-Tate, Fadi W. Abdul-Karim, Chad M. Michener, Peter G. Rose, Justin D. Lathia, Ofer Reizes

Published in: Journal of Ovarian Research | Issue 1/2019

Abstract

Background

Ovarian cancer is the leading cause of gynecologic cancer death in the United States despite effective first-line systemic chemotherapy. Cancer stem cells (CSCs) retain the ability to self-renew and proliferate and may be a means of harboring disease that evades standard treatment strategies. We previously performed a high-throughput screen to assess differential protein expression in ovarian CSCs compared to non-CSCs and observed that Thy-1 was more highly expressed in CSCs. Our primary aim was to validate Thy-1 (CD90) as a cancer stem cell (CSC) marker in epithelial ovarian cancer (EOC), correlate with clinical outcomes, and assess as a potential therapeutic target.

Results

Kaplan Meier (KM) Plotter data were correlated with survival outcomes. Quantitative real-time PCR, flow cytometry, and immunoblots assessed RNA and protein expression. Limiting dilution assays assessed self-renewal capacity and proliferation assays assessed proliferative capacity. RNA in-situ hybridization was performed on patient specimens to assess feasibility. Thy-1 (CD90) is more highly expressed in ovarian CSCs than non-CSCs, in EOC compared to benign ovarian epithelium (P < 0.001), and is highest in serous EOC (P < 0.05). Serous ovarian cancers with high Thy-1 expression have poorer outcomes (median PFS 15.8 vs. 18.3 months, P = 0 < 0.001; median OS 40.1 v. 45.8 months, P = 0.036). Endometrioid ovarian cancers with high Thy-1 have poorer PFS, but no difference in OS (upper quartile PFS 34 v. 11 months, P = 0.013; quartile OS not reached, P = 0.69). In vitro, Thy-1 expression is higher in CSCs versus non-CSCs. EOC cells with high Thy-1 expression demonstrate increased proliferation and self-renewal. Thy-1 knockdown in EOC cells decreases proliferative capacity and self-renewal capacity, and knockdown is associated with decreased expression of stem cell transcription factors NANOG and SOX2. RNA in situ hybridization is feasible in ovarian cancer tissue specimens.

Conclusions

Thy-1 is a marker of ovarian CSCs. Increased expression of Thy-1 in EOC predicts poor prognosis and is associated with increased proliferative and self-renewal capacity. Thy-1 knockdown decreases proliferative and self-renewal capacity, and represents a potential therapeutic target.

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Title: Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer
Authors: Elizabeth V. Connor
Caner Saygin
Chad Braley
Andrew C. Wiechert
Sheelarani Karunanithi
Katie Crean-Tate
Fadi W. Abdul-Karim
Chad M. Michener
Peter G. Rose
Justin D. Lathia
Ofer Reizes
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Ovarian Cancer
Ovarian Cancer
Published in: Journal of Ovarian Research / Issue 1/2019
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-019-0590-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

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