Co-expression of Cancer Stem Cell Markers OCT4 and NANOG Predicts Poor Prognosis in Renal Cell Carcinomas

Many renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined. OCT4 and NANOG were expressed in both the nucleus and the cytoplasm of RCC cells. Coexpression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes. A significant association was found among nuclear coexpression of OCT4 and NANOG, worse PFS in RCC, and the clear cell renal cell carcinomas (ccRCC) subtype. The OCT4-nuclear (high)/NANOG-nuclear (high) phenotype in RCC and ccRCC subtype 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 in patients with renal cancer.