Overexpression of gelsolin in human cervical carcinoma and its clinicopathological significance

Gynecol Oncol. 2011 Jan;120(1):135-44. doi: 10.1016/j.ygyno.2010.10.005. Epub 2010 Oct 28.

Abstract

Objectives: Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited.

Methods: A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer.

Results: The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P<0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P<0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation.

Conclusions: These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Cadherins / metabolism
  • Case-Control Studies
  • Cell Growth Processes / genetics
  • Cell Movement / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Epithelial-Mesenchymal Transition
  • Female
  • Fibronectins / metabolism
  • Gelsolin / biosynthesis*
  • Gelsolin / blood
  • Gelsolin / genetics
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*
  • Vimentin / metabolism

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • CDKN1A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Fibronectins
  • Gelsolin
  • Vimentin
  • Cyclin D1
  • Matrix Metalloproteinase 2