Abstract
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.
Highlights
It is generally proposed that cancer stem cells (CSCs) originate either from progenitor cells that have acquired the ability to self-renew, or adult stem cells that have lost control of proliferation
Our findings suggest that both nuclear expression of Octamer-binding transcription factor 4 (OCT4) and nucleocytoplasmic expressions of NANOG have implications in renal cell carcinoma (RCC) prognosis, conducting further studies with larger sample size and prolonged follow-up time is highly recommended
Our findings further suggest that OCT4 and NANOG coexpression may be valuable biomarkers in predicting the outcome of patients with renal cancer, especially in the clear cell renal cell carcinomas (ccRCC) subtype
Summary
It is generally proposed that CSCs originate either from progenitor cells that have acquired the ability to self-renew, or adult stem cells that have lost control of proliferation. Several studies support the theory that CSCs arise from differentiated tumor cells that have undergone a process of dedifferentiation to become more stem-like[4] It seems that the key regulators in ESC contribute to the pathogenesis of cancers by modulating the differentiation and self-renewal of CSCs5. Octamer-binding transcription factor 4 (OCT4) and NANOG are key regulatory genes that maintain the pluripotency and self-renewal properties of normal stem cells and ESCs6. They induce the expression of each other, regulate cancer progression, and are biomarkers of CSCs7–11. The expression of OCT4 has further been shown in human breast cancer stem-like cells, implicating its involvement in tumorigenesis and self-renewal by activating its downstream target genes, such as NANOG and SOX213. For the first time, we examined the expression patterns and clinical significance of both OCT4 and NANOG as CSC markers in RCC and its subtypes using tissue microarray (TMA) based immunohistochemistry (IHC) technique
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