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Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
  1. Yuan Cao, PhD*,
  2. Yan Yu, MD,,
  3. Xiaolong Chen, MD,,
  4. Fang Ren, PhD*,
  5. Ruitao Zhang, MD*,
  6. Yanyan Jia, MD*,
  7. Zhigang Ren, PhD,,
  8. Ranran Sun, PhD,,
  9. Juan Li, PhD, and
  10. Huirong Shi, PhD*
  1. *Department of Gynecology and Obstetrics,
  2. Department of Infectious Diseases, and
  3. Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  1. Address correspondence and reprint requests to Juan Li, PhD, Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, 1, Jianshe East Rd, Zhengzhou 450052, China. E-mail: ananli1984@126.com; Huirong Shi, PhD, Department of Gynecology and Obstetrics, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Rd, Zhengzhou 450052, China. E-mail: hrshi56@126.com.

Abstract

Objective Ovarian cancer (OC) is the second most lethal gynecological cancer among women throughout the world. Protocadherin-8 (PCDH8) could function as a candidate tumor suppressor. However, the link between PCDH8 and OC development is poorly understood.

Materials and Methods A total of 68 OC patients were retrospectively enrolled. Clinical information was collected and cancer tissues were used for tissue microarray. The PCDH8 expression was determined on tissue microarray by immunohistochemical staining, and PCDH8 protein was detected in cancer tissues and adjacent tissue by western blotting. Human OC cell lines (SKOV-3 and OVCAR-3) were used to assess the effects of PCDH8 overexpression by western blot and real-time PCR analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, wound healing migration assay, colony formation assay and invasion assays were performed to assess the influence of PCDH8 on cell function. Cells with Luc-nonspecific Lentiviral or Luc-Lentiviral with PCDH8 gene were subcutaneously injected into nude mice to observe the effect of PCDH8 gene on tumor growth. Bioluminescence imaging was used to observe tumor volume.

Results We found a low expression of PCDH8 in OC tissues versus the corresponding adjacent tissue. The PCDH8 expression, International Federation of Gynecology and Obstetrics stage, metastasis and recurrence were the independent prognostic factors for over-all survival by multivariate analyses. Furthermore, the patients with recurrence presented a low level of PCDH8 in OC tissues, and patients with advanced tumor stage also had a low PCDH8 expression. Importantly, the low expression of PCDH8 in OC tissues had a poor prognosis with a low overall survival rate. Overexpression of PCDH8 could inhibit OC cell growth/proliferation, migration, invasion, and colony formation in vitro. In vivo experiments also proved that overexpression of PCDH8 could inhibit OC cell growth/proliferation.

Conclusions Protocadherin-8 might be considered as a candidate tumor suppressor and play a crucial role in the progression of OC.

  • Ovarian cancer
  • PCDH8
  • Prognosis
  • Tissue microarray
  • OC - ovarian cancer
  • PCDHs - protocadherins
  • PCDH8 - protocadherin-8
  • TMA - tissue microarray
  • IHC - immunohistochemical

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Footnotes

  • This study was supported by the funds from National Natural Science Foundation of China (81600506), the Medicine Science and Technology research project of Henan province (201702001 and 201702032); Youth innovation fund of the First Affiliated Hospital of Zhengzhou University (J.L. and Z.R.); Joint research fund of the First Affiliated Hospital of Zhengzhou University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences (J.L., R.S., and Z.R.). The funding body has no roles in the design of the study and collection, analysis, and interpretation of data and in writing the article.

  • Y.C. and Y.Y. contributed equally to this work.

  • The authors declare no conflict of interests.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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