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

Int J Gynecol Cancer. 2012 Nov;22(9):1489-96. doi: 10.1097/IGJ.0b013e3182738307.

Abstract

Objective: The objective of this study was to evaluate the prognostic significance of NANOG expression in ovarian serous carcinoma.

Methods: 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."

Results: 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).

Conclusions: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / physiology
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology
  • Humans
  • Middle Aged
  • Nanog Homeobox Protein
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Paclitaxel / therapeutic use
  • Prognosis
  • Survival Analysis
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Paclitaxel