Annexin A1基因表現在口腔鱗狀細胞癌之研究

Abstract

在正常口腔黏膜，ANX A1主要表現在細胞膜，但在分化良好的細胞核亦見其表現；在上皮變異(OED)的病例，則有位置移轉的現象:自細胞膜移向細胞質，或細胞核；而口腔鱗狀上皮細胞癌(OSCC)的病例則，可見ANX A1在細胞核的表現，有增加的現象，其中在OED核的正表現比率為13.64%，即66個病例有9個有正表現；而OSCC則在115個病例中有63個細胞核正表現的現象(54.8%)。其中以Kaplan-Meier曲線分析，顯示OSCC的細胞核陽性表現與較短的存活率，在統計上有意義的相關(P:0.00036)。多變數分析(stepwise multivariate logistic-regression model)，則顯示出ANX A1核染色可用來做一為較差存活的指標。另外，在口腔鱗狀上皮細胞癌細胞株SAS，投予肝生長因子(HGF)可誘發ANX A1蛋白質自細胞膜質移向細胞核。而以PI3K的抑制劑LY294002幾乎可以完全抑制(88.3%)由HGF所引起的ANX A1之細胞核移轉。

To investigate whether annexin A1 (ANXA1) expression is a marker in predicting the prognosis of oral cancer patients. We immunohistochemically examined the expression of ANXA1 in 66 cases of oral epithelial dysplasia (OED) and 115 cases of oral squamous cell carcinoma (OSCC). The results were correlated with the clinicopathological parameters of tumors and overall patient survival. In normal oral mucosa, ANXA1 staining was predominantly located on the cell membrane. In OED and OSCC specimens, membranous staining decreased, whereas nuclear staining increased. Positive nuclear staining was observed in 9 of 66 (13.64%) OED cases and 63 of 115 (54.8%) OSCCs. Kaplan–Meier curves showed that OSCC patients with ANXA1 nuclear staining had significantly shorter overall lengths of survival (P¼0.00036 by the log-rank test). Multivariate analysis showed that ANXA1 nuclear staining is a significant predictor of poor overall survival. And oral cancer SAS cells treated with hepatocyte growth factor (HGF) can induce ANXA1 protein translocation from cytoplasm to nucleus. Cells pretreated with LY294002 (PI3K inhibitor) almost completely inhibited (88.3% inhibition) HGF-mediated ANXA1 nuclear translocation. The nuclear localization of ANXA1 protein is a frequent event and could be used as a prognostic factor in OSCC.