The predictive potential and oncogenic effects of HOXC8 expression on osteosarcoma

Tumour Biol. 2016 Nov;37(11):14961-14967. doi: 10.1007/s13277-016-5384-4. Epub 2016 Sep 20.

Abstract

Homeobox C8 (HOXC8) has been implicated in cell growth, migration, and metastasis of various cancers, yet its role in osteosarcoma remains to be explored. In the present study, resected osteosarcoma specimens from 50 patients were enrolled to evaluate the expression of HOXC8 protein by immunohistochemistry (IHC). In vitro and in vivo assays were used to determine the effect of HOXC8 on cell growth, migration, and tumor growth. HOXC8 expression was observed in 31 (62.0 %) of the 50 primary tumors and significantly associated with poorly or un-differentiated specimens (P = 0.031) and larger tumor size (P = 0.049). Survival analysis demonstrated that HOXC8 is a candidate predictive factor in predicting patients' outcome and chemotherapeutic effect. HOXC8 knockdown led to inhibition of tumor cell proliferation and migration in vitro by inhibiting MMP-9 expression and tumor growth in vivo. Our results strongly suggest that HOXC8 is involved in the tumorigenesis of osteosarcoma and might serve as a novel predictor for patients' outcome.

Keywords: Chemotherapeutic effect; HOXC8; Immunohistochemistry; Osteosarcoma; Prognosis.

MeSH terms

  • Adolescent
  • Animals
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Osteosarcoma / pathology*
  • RNA Interference
  • RNA, Small Interfering
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • HOXC8 protein, human
  • Homeodomain Proteins
  • RNA, Small Interfering
  • MMP9 protein, human
  • Matrix Metalloproteinase 9