Introduction:

The global yearly incidence and mortality of cervical cancer are 471,000 annual new cases and 233,000 deaths. Almost 80% cases occur in less developed countries, where it accounts for 15% of cancer in women. Cervical carcinoma ranks as the leading malignancy of genital tract malignancy in the developing countries. The recurrence indicate poor prognosis while the clinicopathological risk factors exist. In order to identify the potential molecular biomarker, proteomic analysis was performed and gesolin protein was selected.

Materials and Methods:

The plasma from normal healthy and cervical cancer, and tissue of cervical cancer plus adjacent normal tissue were collected for Western blotting assay, enzyme-linked immunosorbent assay (ELISA) or immunohistochemical stain (IHC). One hundred and twenty four patients with cervical cancers underwent surgical management were enrolled to evaluate IHC Histoscore of gesolin according to the multiply of immunoreactivity and involved percentage. The Transwell assay was conducted for cell migration analysis in HeLa cell line. The statistical analysis include independent t tests, Kaplan-Meier method using the log-rank test and the Cox proportional hazard model Receiver operating characteristics (ROC) curve analysis was used to determine cut-off points of the predictive parameters in univariate analysis.

Results:

The Western blot and ELISA assay both demonstrated the overexpression of plasma gelsolin in cases with cervical cancer rather than normal population, and with staged III/IV rather than stage I/II cases, In addition, gelsolin protein level also increased in conditional medium of cultured HeLa cell. Thus in vitro cell migration assay revealed decreased cell numbers while adding the gelsolin neutralizing antibody or small interference RNA compared with adding mock, non-specific antibody or Luciferase-shRNA. The other clinical parameters including stage, tumor size and lymph node status also put into consideration. The best cut-off point of gesolin Histosore to clarify the recurrence by ROC curve analysis is 115. The gelsolin Histosore (≤ 115 vs > 115, P= 0.018) and lymph node metastasis (no vs yes, P<0.001) play important prognostic role in recurrence by multivariate analysis.

Conclusion:

Overexpression of plasma and cytoplasmic gelsolin protein in cervical cancer promote cell migration by binding to actin cytoskeleton for rearrangement and cell motility. Among the clinicopathological parameters, the gelsolin overexpression and lymph node metastasis disclosed the recurrence-free survival impact by multivariate analysis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1740.