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      Prognostic impact of the cancer stem cell-related marker NANOG in ovarian serous carcinoma.

      International Journal of Gynecological Cancer
      Adult, Aged, Antineoplastic Agents, therapeutic use, Cell Line, Tumor, Cystadenocarcinoma, Serous, diagnosis, genetics, mortality, pathology, Drug Resistance, Neoplasm, drug effects, Female, Gene Expression Regulation, Neoplastic, physiology, Homeodomain Proteins, metabolism, Humans, Middle Aged, Neoplastic Stem Cells, Ovarian Neoplasms, Paclitaxel, Prognosis, Survival Analysis, Tumor Markers, Biological, Young Adult

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          Abstract

          The objective of this study was to evaluate the prognostic significance of NANOG expression in ovarian serous carcinoma. The expression of NANOG was evaluated in 6 ovarian carcinoma cell lines, paclitaxel-resistant SKOV3 cells, and SKOV3 spheroid cells with semiquantitative reverse transcription-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 24 with ovarian serous cystadenoma. Each sample was scored based on signal intensity and proportion, and a score greater than 4 was considered "positive." 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 with that in the SKOV3 cells. NANOG expression was positive in 21.6% of 74 ovarian serous carcinoma tissues, but none of the ovarian serous cystadenoma tissues were positive. Positive NANOG expression was associated with residual tumor size after surgery (P = 0.032). 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 and 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 involved in the mechanism of chemoresistance.

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