Open Access

ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation

  • Authors:
    • Qun Liu
    • Heshu Liu
    • Lina Li
    • Xiaomei Dong
    • Xiaoli Ru
    • Xiana Fan
    • Tao Wen
    • Jian Liu
  • View Affiliations

  • Published online on: November 14, 2019     https://doi.org/10.3892/ijo.2019.4913
  • Pages: 219-231
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The oncogene ATPase family AAA domain‑​containing protein 2 (ATAD2) has been demonstrated to promote malignancy in a number of different types of tumor; however, its expression and role in ovarian cancer (OC) remain unknown. In the present study, it was demonstrated that ATAD2 acts as both a marker and a driver of cell proliferation in OC. Immunohistochemistry (IHC) and bioinformatics analyses were used to evaluate ATAD2 expression in OC, and multi‑omics integrated analyses were used to dissect which factor resulted in its upregulation. Multiplex IHC assay was used to reveal the specific expression of ATAD2 in proliferating OC cells. CRISPR‑Cas9‑mediated gene editing was performed to investigate the effect of ATAD2 deletion on OC proliferation. The results demonstrated that ATAD2 is elevated in primary OC tissues compared with the adjacent normal tissue and metastases from the stomach. Genetic copy number amplification is a primary cause resulting in upregulation of ATAD2, and this was most frequently observed in OC. High ATAD2 expression was associated with advanced progression and predicted an unfavorable prognosis. ATAD2 could be used to identify cases of OC with a high proliferation signature and could label proliferating cells in OC. CRISPR‑Cas9‑mediated ATAD2 deletion resulted in a significant decrease in both cell proliferation and colony formation ability. Mechanistically, ATAD2‑knockdown resulted in deactivation of the mitogen‑activated protein kinase (MAPK) pathways, particularly the JNK‑MAPK pathway, resulting in suppression of proliferation. Collectively, the data from the present study demonstrated that the ATD2 gene was frequently amplified and protein expression levels were upregulated in OC. Therefore, ATAD2 may serve as an attractive diagnostic and prognostic OC marker, which may be used to identify patients with primary OC, whom are most likely to benefit from ATAD2 gene‑targeted proliferation intervention therapies.
View Figures
View References

Related Articles

Journal Cover

January 2020
Volume 56 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Liu, Q., Liu, H., Li, L., Dong, X., Ru, X., Fan, X. ... Liu, J. (2020). ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation. International Journal of Oncology, 56, 219-231. https://doi.org/10.3892/ijo.2019.4913
MLA
Liu, Q., Liu, H., Li, L., Dong, X., Ru, X., Fan, X., Wen, T., Liu, J."ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation". International Journal of Oncology 56.1 (2020): 219-231.
Chicago
Liu, Q., Liu, H., Li, L., Dong, X., Ru, X., Fan, X., Wen, T., Liu, J."ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation". International Journal of Oncology 56, no. 1 (2020): 219-231. https://doi.org/10.3892/ijo.2019.4913