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Tumor Biology

, Volume 35, Issue 12, pp 11845–11849 | Cite as

Overexpression of GOLPH3 protein is associated with worse prognosis in patients with epithelial ovarian cancer

  • Yingchun Ma
  • Xiuxia Wang
  • Yuanhong Wu
  • Binghui Sun
  • Hongtao Lv
  • Fengnian Rong
  • Xiaoxia Zheng
Research Article

Abstract

Golgi phosphoprotein 3 (GOLPH3) has important roles in the pathogenesis of cancer, and overexpression of GOLPH3 has been found in several kinds of cancers. However, the relationship between GOLPH3 overexpression and prognosis in patients with epithelial ovarian cancer remains unknown. This study aimed to investigate the relationship between GOLPH3 overexpression and overall survival in patients with epithelial ovarian cancer. The expression of GOLPH3 protein in tumor tissue was evaluated using immunohistochemistry. Seventy-five patients with epithelial ovarian cancer with the data of GOLPH3 expression and follow-up were included. GOLPH3 overexpression was significantly associated with advanced stage, histology, high grade, and lymph node metastases (P < 0.05). Kaplan-Meier analysis showed that patients with GOLPH3 overexpression had significantly poorer overall survival than those with low expression of GOLPH3 (log-rank P < 0.001). In the multivariate Cox proportional hazards analysis, GOLPH3 overexpression was independently associated with poorer overall survival (hazard ratio [HR] = 3.60; 95 % confidence interval (CI0 1.14–11.33, P = 0.03). Therefore, overexpression of GOLPH3 protein is closely related to poorer prognosis in patients with epithelial ovarian cancer.

Keywords

Epithelial ovarian cancer Golgi phosphoprotein 3 Prognosis 

Notes

Acknowledgments

None.

Conflicts of interest

None

References

  1. 1.
    Cho KR, Shih IM. Ovarian cancer. Annu Rev Pathol. 2009;4(1):287–313.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Wang Y, Wang D, Ren M. Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a meta-analysis. Tumor Biol. 2014;35(1):33–8.CrossRefGoogle Scholar
  3. 3.
    Kandalaft LE, Motz GT, Duraiswamy J, Coukos G. Tumor immune surveillance and ovarian cancer: lessons on immune mediated tumor rejection or tolerance. Cancer Metastasis Rev. 2011;30(1):141–51.PubMedCrossRefGoogle Scholar
  4. 4.
    Wu XJ, Yuan P, Li ZY, Bu ZD, Zhang LH, Wu AW, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patietns with ovarian metastasis and peritoneal dissemination. Tumor Biol. 2013;34(1):463–9.CrossRefGoogle Scholar
  5. 5.
    Clarke-Pearson DL. Clinical practice. Screening for ovarian cancer. N Engl J Med. 2009;361(2):170–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Cooke SL, Brenton JD. Evolution of platinum resistance in high-grade serous ovarian cancer. Lancet Oncol. 2011;12(12):1169–74.PubMedCrossRefGoogle Scholar
  7. 7.
    Kulasingam V, Pavlou MP, Diamandis EP. Integrating high-throughput technologies in the quest for effective biomarkers for ovarian cancer. Nat Rev Cancer. 2010;10(5):371–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Karam AK, Karlan BY. Ovarian cancer: the duplicity of ca125 measurement. Nat Rev Clin Oncol. 2010;7(6):335–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Chen MB, Wu XY, Yu R, Li C, Wang LQ, Shen W, et al. P53 status as a predictive biomarker for patients receiving neoadjuvant radiation-based treatment: a meta-analysis in rectal cancer. PLoS ONE. 2012;7(9):e45388.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Kemal Y, Demirag G, Ekiz K, Yucel I. Mean platelet volume could be a useful biomarker for monitoring epithelial ovarian cancer. J Obstet Gynaecol. 2014;15(1):1–4.Google Scholar
  11. 11.
    Caceres-Gorriti KY, Carmona E, Barres V, Rahimi K, Letouneau IJ, Tonin PN, et al. RAN necleo-cytoplasmic transport and mitotic spindle assembly partners XPO7 and TPX2 are new prognostic biomarkers in serous epithelial ovarian cancer. PLoS ONE. 2014;9(3):e91000.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Chen WT, Gao X, Han XD, Zheng H, Guo L, Lu RQ. HE4 as a serum biomarker for ROMA prediction and prodiction and prognosis of epithelial ovarian cancer. Asian Pac J Cancer Prev. 2014;15(1):101–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Scott KL, Chin L. Signaling from the golgi: mechanisms and models for golgi phosphoprotein 3-mediated oncogenesis. Clin Cancer Res. 2010;16(8):2229–34.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, et al. Golph3 modulates mtor signalling and rapamycin sensitivity in cancer. Nature. 2009;459(7250):1085–90.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Dippold HC, Ng MM, Farber-Katz SE, Lee SK, Kerr ML, Peterman MC, et al. Golph3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the golgi to promote budding. Cell. 2009;139(2):337–51.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Farber-Katz SE, Dippold HC, Buschman MD, Peterman MC, Xing M, Noakes CJ, et al. DNA damage triggers golgi dispersal via DNA-PK and GOLPH3. Cell. 2014;156(3):413–27.PubMedCrossRefGoogle Scholar
  17. 17.
    Xue Y, Wu G, Liao Y, Xiao G, Ma X, Zou X, et al. Golph3 is a novel marker of poor prognosis and a potential therapeutic target in human renal cell carcinoma. Br J Cancer. 2014;110(9):2250–60.PubMedCrossRefGoogle Scholar
  18. 18.
    Zeng Z, Lin H, Zhao X, Liu G, Wang X, Xu R, et al. Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the foxo1 transcription factor. Clin Cancer Res. 2012;18(15):4059–69.PubMedCrossRefGoogle Scholar
  19. 19.
    Hua X, Yu L, Pan W, Huang X, Liao Z, Xian Q, et al. Increased expression of golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer. Diagn Pathol. 2012;7(1):127.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Zhou J, Xu T, Qin R, Yan Y, Chen C, Chen Y, et al. Overexpression of golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis. J Neurooncol. 2012;110(2):195–203.PubMedCrossRefGoogle Scholar
  21. 21.
    Hu BS, Hu H, Zhu CY, Gu YL, Li JP. Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer. Tumour Biol. 2013;34(1):515–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Ma Y, Ren Y, Zhang X, Lin L, Liu Y, Rong F, et al. High GOLPH3 expression is associated with a more aggressive behavior of epithelial ovarian carcinoma. Virchows Arch. 2014;464(4):443–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Farber-Katz SE, Dippold HC, Buschman MD, Peterman MC, Xing M, Noakes CJ, et al. DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3. Cell. 2014;156(3):413–27.PubMedCrossRefGoogle Scholar
  24. 24.
    Li H, Guo L, Chen SW, Zhao XH, Zhuang SM, Wang LP, et al. GOLPH3 overexpression correlates with tumor progression and poor prognosis in patients with clinically N0 oral tongue cancer. J Transl Med. 2012;10(1):168.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Cao J, Cai J, Huang D, Han Q, Chen Y, Yang Q, et al. Mir-335 represents an independent prognostic marker in epithelial ovarian cancer. Am J Clin Pathol. 2014;141(3):437–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Liu T, Gao H, Chen X, Lou G, Gu L, Yang M, et al. TNFAIP8 as a predictor of metastasis and a novel prognostic biomarker in patients with epithelial ovarian cancer. Br J Cancer. 2013;109(6):1685–92.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Lee JY, Myung SK, Song YS. Prognostic role of cyclooxygenase-2 in epithelial ovarian cancer: a meta-analysis of observational studies. Gynecol Oncol. 2013;129(3):613–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Taft MH, Behrmann E, Munske-Weidemann LC, Thiel C, Raunser S, Manstein DJ. Functional characterization of human myosin-18A and its interaction with F-actin and GOLPH3. J Biol Chem. 2013;288(42):30029–41.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Chang WL, Chang CW, Chang YY, Sung HH, Lin MD, Chang SC, et al. The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins. Development. 2013;140(13):2798–807.PubMedCrossRefGoogle Scholar
  30. 30.
    Sechi S, Colotti G, Belloni G, Mattei V, Frappaolo A, Raffa GD, et al. GOLPH3 is essential for contractile ring formation and Rab11 localization to the cleavage site during cytokinesis in Drosophila melanogaster. PLoS Genet. 2014;10(5):e1004305.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Rafnar T, Gudbjartsson DF, Sulem P, Jonasdottir A, Sigurdsson A, Besenbacher S, et al. Mutations in BRIP1 confer high risk of ovarian cancer. Nat Genet. 2011;43(11):1104–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Glienke W, Maute L, Wicht J, Bergmann L. The dual PI3K/mTOR inhibitor NVP-BGT226 induces cell cycle arrest and regulates Survivin gene expression in human pancreatic cancer cell lines. Tumor Biol. 2012;33(3):757–65.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Gynecology and Obstetrics, Shandong Qianfoshan HospitalShandong University, JinanShandongPeople’s Republic of China
  2. 2.Department of Obstetrics and GynecologyLiaocheng People’s Hospital, LiaochengShandongPeople’s Republic of China
  3. 3.Department of Gynecology and ObstetricsJinan Shizhong People’s HospitalShandongPeople’s Republic of China
  4. 4.Department of Gynecology and ObstetricsJinan Maternity and Child Healthcare HospitalShandongPeople’s Republic of China

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