Prognostic significance of NANOG in ovarian serous carcinoma

Abstract

NANOG, a key transcription factor in embryonic stem cell self-renewal and pluripotency, plays an important role in solid tumor development. The purpose of this study was to evaluate the prognostic significance of NANOG expression in ovarian serous carcinoma. The expression of NANOG was evaluated in vitro in 6 ovarian carcinoma cell lines, paclitaxel-resistant SKOV3 (SKOV3-PR) cells, and SKOV3 spheroid cells with reverse transcription of mRNA, semi-quantitative polymerase chain reaction, and Western blotting. NANOG expression was also measured immunohistochemically in a tissue microarray containing ovarian tissues from 74 patients with ovarian serous carcinoma and 4 with ovarian serous cystadenoma. Each sample was scored based on signal intensity and proportion, and a score greater than 4 was considered “positive”. The correlation of NANOG expression with clinicopathological characteristics was assessed in terms of the following parameters: stage, age, cancer antigen-125, grade, ascites, lymph node status, and survival. NANOG mRNA expression was variable in different ovarian cancer cell lines. The mRNA level of NANOG was increased in the paclitaxel-resistant SKOV3 cells and SKOV3 spheroid cells compared to that in the SKOV3 cells. NANOG expression was positive in 21.6% of 74 ovarian serous carcinoma tissue samples, but none of the ovarian serous cystadenoma tissue samples were positive. Positive NANOG expression was associated with tumor grade (P = 0.073), but not with age, tumor stage, cytological positivity, nodal involvement, ascites, tumor size, or CA-125. The overall survival of the patients with positive NANOG expression was poorer than that of the patients with negative NANOG expression (P = 0.020). In patients with stage I or II disease, positive NANOG expression was independently associated with shorter overall survival compared with negative NANOG expression (40 vs. 120 months, respectively; P = 0.031). Positive NANOG expression is associated with poor prognosis of ovarian serous carcinoma. NANOG has potential as a predictor of survival for patients with ovarian carcinomas and may be involve in the mechanism of chemoresistance.