The Expression Of ALDH1 And CD133 And The Impact To Migration And Invasion In Epithelial Ovarian Cancer

Purpose:We are aimed at evaluating the function of the expression of ALDH1 and/or CD133 in disease progression and clinical prognosis of patients with ovarian cancer, moreover, assessing the effect of ALDH1 and / or CD133 expression to ovarian cancer cells biological behavior, and its significance as the ovarian cancer stem cell markers. Methods:1. We collected samples of 205 epithelial ovarian cancer tissues, 30 benign ovarian tumor tissues and 30 normal ovarian tissues from Hunan Cancer Hospital during from 2011 to 2014. Immunohistochemistry staining method was used to detect the expression of ALDH1 and CD133, and evaluate the relationship between its expression and clinicopathological characteristics and even the prognosis impact of ovarian cancer patients.2. Flow cytometry was applied to sort different groups of cells with ALDH1~+ and ALDH1~-,CD133~+ and CD133~-,ALDH1~+CD133~+ and ALDH1~-CD133~-.Then scratch assay, transwell invasion, migration assay and clonogenic assay were used to detect the migration, invasion and clone forming ability of the above different subpopulations of cells. Results:1. The expression of ALDH1 and CD133 in normal ovary tissue shows a lower level compared with epithelial ovarian cancer tissue(P < 0.05),but there are no statistical significance when contrasted with benign ovarian tumor(P <>0.05); In the comparison between epithelial ovarian cancer and benign ovarian cancer, the expression of CD133 has significant difference(P < 0.05) while the ALDH1 has no diffenence(P > 0.05).2. There is a significant correlation between ALDH1 expression and the histological grade, lymph node metastasis, preoperative CA125 level as well as the MDACC type(P < 0.05). CD133 expression is positively related with FIGO stage and lymph node metastasis(P < 0.05).3. Kaplan Meier survival analysis showed that compared to ALDH1~- and CD133~- group, the progression-free survival rate and overall survival rate of ALDH1 + and CD133 + group were significantly reduced(P < 0.05). At the same time, ALDH1~+CD133~+ ovarian cancer patients with overall survival rate and progression-free survival rate was significantly lower than the non double positive group(P < 0.05).According to Cox multivariate analysis, the risk factors of progression-free survival are the positive expression of CD133 and ALDH1,lymph node metastasis(P < 0.05). While the later FIGO staging, ALDH1 and CD133 positive expression are the risk factors of overall survival of ovarian cancer patients(P < 0.05).4. Spearman correlation analysis showed that ALDH1 and CD133 proteins were positively correlated(P<0.05, r=0.169).5.ALDH1~+ versus ALDH1~-, CD133~+ versus CD133~- and ALDH1~+CD133~+ versus ALDH1~-CD133~-, the invasion, migration and cell clones number of forming ability of the former(ALDH1~+, CD133~+ and ALDH1~+CD133~+) were obviously enhanced respectively(P < 0.05). Conclusions:1. ALDH1 and CD133 are highly expressed in epithelial ovarian cancer, and their high expression are negative correlation with the prognosis of ovarian cancer patients,the combined detection of ALDH1 and CD133 may be a molecular marker set for poor prognosis of ovarian cancer patients.2. The expression of ALDH1 and CD133 in epithelial ovarian cancer are relatively positive correlated.3. ALDH1 and CD133 can promote the proliferation,invasion and metastasis of epithelial ovarian cancer cells,which suggesting that they may have stem cell-like characteristics.