Abstract
IntroductionNANOG is a transcription factor involved in embryonic pluripotency maintenance. It has also been shown that it has a mitogenic function in adult epithelial tissues. Overexpression of NANOG in mice causes hyperplasia, increased proliferation and aneuploidy. In humans, it has been found to be frequently aberrantly expressed in a variety of cancers, including head and neck squamous cell carcinomas (HNSCC). This overexpression has been associated with chemoresistance, epithelial to mesenchymal transformation (EMT) and poor clinical outcome. Even if there is enough evidence supporting the oncogenic role of NANOG, its role in the early stages of tumorigenesis in HNSCC has not been assessed. This study investigates for the first time the role of NANOG expression in early stages of laryngeal tumourigenesis and its potential utility as cancer risk marker.Material and methodsNANOG protein expression was evaluated by immunohistochemistry in a group of 82 patients from Asturias with laryngeal precancerous lesions, and correlated with clinicopathological parameters and laryngeal cancer risk. Results were validated in an independent cohort of 86 patients from Barcelona.Results and discussionsNANOG expression was detected in the cytoplasm by immunohistochemistry in 49 (60%) of 82 laryngeal dysplasias, whereas expression was negligible in patient-matched normal epithelia. Strong NANOG expression was found in 22 (27%) lesions. 24 of the patients (29%) developed an invasive carcinoma on the site of the lesion in the following months. No significant differences between the group that developed cancer and the one that did not were found concerning age (p=0.703), smoking (p=0.316) or histopathological diagnosis (p=0.748). Cytoplasmic expression of NANOG showed the most robust association with laryngeal cancer risk (p=0.007). Patients with a strong expression of cytoplasmic NANOG had a higher risk of getting laryngeal cancer (HR=1.826, p=0.003). Similar trends were obtained using the validation cohort. Our findings show NANOG is frequently overexpressed in laryngeal dysplasias but not in adjacent normal epithelia. Strong expression of cytoplasmic NANOG significantly correlated with a higher cancer incidence, showing a superior predictive power than histological classification, which is the current gold standard to determine cancer risk.ConclusionTogether our studies uncover a novel role for NANOG expression in laryngeal tumourigenesis, and its unprecedented application as biomarker for cancer risk assessment.
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