Sonic Hedgehog is a novel prognostic biomarker in patients with oral squamous cell carcinoma

 Piotr Cierpikowski, Anna Lis-Nawara, Julia Bar

Abstract:

Recent studies revealed that Sonic Hedgehog (SHH) signaling pathway plays an important role in initiation and tumor progression in various malignancies, however, its role in oral squamous cell carcinoma (OSCC) remains unclear. The objective of this study was to investigate the prognostic significance of SHH expression in patients with OSCC in relation to p53 protein expression and human papillomavirus (HPV) presence. SHH, p53, HPV expression was analyzed in surgical specimens from 70 patients with primary OSCC by immunohistochemistry (IHC) and correlated with clinicopathological parameters. The presence of SHH, p53, HPV was found in 51/70 (72.9%), 32/70 (45.7%), 11/70 (15.7%) cases, respectively. No correlation between SHH, p53 overexpression, and HPV presence was found. SHH expression was associated with tumor stage (p=0.026). P53 immunoreactivity correlated with tumor grade (p=0.040). By Kaplan-Meier analysis, SHH expression was significantly associated with shorter overall survival (p=0.005). Multivariate cox regression analysis showed that SHH was an independent prognostic factor for overall survival (HR=2.93; 95% CI=1.40–6.13; p=0.004). Our findings revealed that the SHH signaling pathway contributes to the poor survival of patients with OSCC and should be considered as a new prognostic biomarker in patients with OSCC. Inhibition of the SHH pathway may be used as a new potential target in cancer therapy.