A novel biomarker ARMc8 promotes the malignant progression of ovarian cancer

Hum Pathol. 2015 Oct;46(10):1471-9. doi: 10.1016/j.humpath.2015.06.004. Epub 2015 Jun 16.

Abstract

Ovarian cancer is the most lethal gynecologic malignancy worldwide, and the survival rates have remained low in spite of medical advancements. More research is dedicated to the identification of novel biomarkers for this deadly disease. The association between ARMc8 and ovarian cancer remained unraveled. In this study, immunohistochemical staining was used to examine ARMc8 expression in 247 cases of ovarian cancer, 19 cases of borderline ovarian tumors, 41 cases of benign ovarian tumors, and 9 cases of normal ovarian tissues. It was shown that ARMc8 was predominantly located in the cytoplasm of tumor cells, and its expression was up-regulated in the ovarian cancer (61.9%) and the borderline ovarian tumor tissues (57.9%), in comparison with the benign ovarian tumors (12.2%; P < .05) and the normal ovarian tissues (11.1%; P < .05). In ovarian cancer, ARMc8 expression was closely related to International Federation of Gynecology and Obstetrics stages (P = .002), histology grade (P < .001), lymph node metastasis (P = .008), and poor prognosis (P < .001). Univariate and multivariate Cox analyses revealed that ARMc8 expression was an independent prognostic factor for ovarian cancer (P = .039 and P = .005). In addition, ARMc8 could promote the invasion and migration of ovarian cancer cells. Overexpressing ARMc8 enhanced the invasion and metastasis capacity of ARMc8-low Cavo-3 cells (P < .001), whereas interfering ARMc8 significantly reduced cell invasion and metastasis in ARMc8-high SK-OV-3 cells (P < .001). Furthermore, ARMc8 could up-regulate matrix metalloproteinase-7 and snail and down-regulate α-catenin, p120ctn, and E-cadherin. Collectively, ARMc8 may enhance the invasion and metastasis of ovarian cancer cells and likely to become a potential therapeutic target for ovarian cancer.

Keywords: ARMc8; Invasion; Metastasis; Ovarian cancer; α-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Armadillo Domain Proteins / analysis
  • Armadillo Domain Proteins / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Cells, Cultured
  • Cystadenocarcinoma / mortality
  • Cystadenocarcinoma / pathology*
  • Cystadenoma / mortality
  • Cystadenoma / pathology*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Transfection

Substances

  • ARMC8 protein, human
  • Armadillo Domain Proteins
  • Biomarkers, Tumor