Co-expression of Cancer Stem Cell markers OCT4 and NANOG predicts poor prognosis in Renal Cell Carcinomas

Purpose Cancer stem cells (CSCs), a small subset of cancer cells, are known with stem cell properties with stem cell properties which are responsible for tumor growth,recurrence and metastatic progression. This study aimed to evaluate the expression patterns and clinical signiï پcance of octamer-binding transcription factor 4 (OCT4)and NANOG as the key stem cell factors in RCC. Methods One hundred and eighty six RCC tissues composed of clear cell renal cell carcinomas (ccRCC), papillary renal cell carcinomas (pRCC) and chromophobe renal cell carcinomas (chRCC), were immunostained on a tissue microarray(TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation between the expression of these markers and the clinicopathological variables as well as disease specific (DSS) and progression free survival (PFS) were then analyzed. Results Immunohistochemistry analysis showed that OCT4 and NANOG were expressed in both the nuclei and the cytoplasm of RCC cells. Co-expression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes, tumor size and microvascular invasion. (P-values 0.012, 0.016, and 0.030, respectively). A significant association was found between nuclear co-expression of OCT4 and NANOG and worse PFS in RCC; this correlation remained significant in patients with ccRCC subtype. (P-values 0.004 and 0.040, respectively). The higher nuclear expression of OCT4, also cytoplasmic NANOG overexpression, was separately associated withworse PFS in RCC (P-values 0.003 and 0.010, respectively). Cox regression analysis showed that cytoplasmic expression of NANOG was an independent poor prognostic factor for PFS with hazard ratios of 2.14 and 2.23 and P-values, 0.024 and 0.033, respectively.Conclusions The OCT4-nuclear high/NANOG-nuclear high phenotype in RCC and ccRCCsubtype indicated aggressive tumor behavior and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence and metastasis. Cytoplasmic expression of NANOG could be considered as a novel independent prognostic predictor for patients with renal cancer.

کلیدواژه ها:

cancer stem cell (CSC) ، renal cell carcinoma (RCC) ، OCT4 ، NANOG ، tissue microarray (TMA)