Abstract
NANOG protein, a transcription factor expressed in embryonic stem cells, is overexpressed in tumor development. Although studies investigating the function of NANOG in cancer have shown that it plays several roles, such as in cell proliferation, invasion and metastasis, the overall function of NANOG in cancer cells has remained elusive. In the present study, NANOG expression in oral squamous cell carcinoma (OSCC) was examined to determine its potential clinical significance. The expression of NANOG protein was assessed in 60 patients with OSCC by immunohistochemistry, and its correlation with clinicopathological factors and metastasis was evaluated. NANOG protein levels in human OSCC cell lines were determined by western blotting and immunofluorescence staining. NANOG protein expression was identified in 52 cases (86.7%) and expression levels were higher in primary foci of poorly differentiated OSCC than in those of well-differentiated OSCC, indicating that NANOG expression is associated with OSCC differentiation. Regardless of the differentiation levels of primary foci, NANOG expression levels in metastatic foci were extremely high. In addition, NANOG expression in metastatic foci was maintained at high levels following preoperative adjuvant therapy. Furthermore, NANOG protein was detected at an identical level in human OSCC cell lines. These data indicate that NANOG-expressing OSCC cells tend to metastasize and that metastatic tumors expressing NANOG may be resistant to preoperative adjuvant therapy, including chemoradiation. Thus, assessment of NANOG expression may assist the strategy for treatment of OSCC metastasis.
Highlights
Head and neck squamous cell carcinoma, which includes oral squamous cell carcinoma (OSCC), is the sixth most prevalent malignancy worldwide [1,2]
NANOG protein was clearly stained in the nuclei of cells at various levels in OSCC specimens
In OSCC cell lines, NANOG protein levels were analyzed in SAS, HSC‐3 and HSC‐4 cells derived from tongue SCCs by western blotting and immunofluorescence staining
Summary
Head and neck squamous cell carcinoma, which includes oral squamous cell carcinoma (OSCC), is the sixth most prevalent malignancy worldwide [1,2]. Previous studies report variable NANOG expression, from undetectable to extremely high levels, in OSCC samples. NANOG expression may be associated with patient survival. Elevated NANOG expression has been found to be associated with a poor prognosis, advanced stage and medially‐to‐poorly differentiated OSCC [14,15]. Based on these observations, NANOG may be a useful prognosis factor. The correlation among NANOG expression, differentiation and metastasis in OSCC remains unclear. NANOG expression in OSCC specimens was examined by immunohistochemistry. The association between NANOG expression and differentiation, metastatic potency and resistance of OSCC to preoperative adjuvant therapy was evaluated
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