Abstract
NANOG is a master regulator of embryonic stem cell pluripotency, found to be frequently aberrantly expressed in a variety of cancers, including laryngeal carcinomas. 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. NANOG protein expression was evaluated by immunohistochemistry using two large independent cohorts of patients with laryngeal precancerous lesions, and correlated with clinicopathological parameters and laryngeal cancer risk. NANOG expression was detected 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 and was established as cut-off point, showing the most robust association with laryngeal cancer risk (P = 0.003) superior to the histological classification (P = 0.320) the current gold standard in the clinical practice. Similar trends were obtained using a multicenter validation cohort of 86 patients with laryngeal dysplasia. Our findings uncover a novel role for NANOG expression in laryngeal tumourigenesis, and its unprecedented application as biomarker for cancer risk assessment.
Highlights
The role of NANOG in the early stages of HNSCC tumourigenesis and its possible implication in malignant transformation and acquisition of an invasive phenotype remains to be determined
Immunohistochemical analysis of NANOG protein expression was performed on a set of 82 laryngeal dysplasias
We recently reported that NANOG is frequently aberrantly expressed in squamous cell carcinomas, including HNSCC5
Summary
The role of NANOG in the early stages of HNSCC tumourigenesis and its possible implication in malignant transformation and acquisition of an invasive phenotype remains to be determined This prompted us to investigate NANOG protein expression in laryngeal tumourigenesis using a large series of 82 laryngeal precancerous lesions to establish correlations with clinicopathological parameters and the risk of progression to invasive carcinoma. This work unveils the clinical utility of NANOG expression as cancer risk marker in patients with laryngeal dysplasias, showing superior predictive power to histology. These results were further confirmed using an independent multicenter cohort of 86 patients with laryngeal premalignancies
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