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

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 HPV (Human Papilloma Virus) 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.

The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

“…Several studies have demonstrated that the HH pathway plays a crucial role in tumor growth and invasion in HNSCC. Therefore, increased expression of SHH, PTCH1, SMO, GLI1, GLI2, and GLI3 was detected significantly more frequently in advanced HNSCC tumors [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. In most cases, progressing HNSCC invades the mandible or maxilla, what leads to bone destruction.…”

“…The correlation between the expression of HH proteins and prognosis in patients with HNSCC is still not well established. Most studies revealed that increased SHH, PTCH1, SMO, and GLI1 expression are significantly correlated with worse OS [ 50 , 57 , 59 , 60 , 67 , 68 ]. Contrary to these results, Enzenhofer et al observed better OS in HPV-negative HNSCC patients with GLI1 and GLI2 overexpression [ 69 ].…”

“…Additionally, SHH, GLI1, and SMO overexpression were significantly correlated with tumor recurrence and shorter disease-free survival (DFS) [ 54 , 67 , 68 ]. However, only two of all the studies were confirmed by multivariate COX regression analysis, indicating that the overexpression of GLI1 and SHH may serve as independent poor prognostic biomarkers in HNSCC [ 57 ]. Further studies with larger cohorts are required to define the prognostic significance of the HH pathway components in patients with HNSCC.…”

“…Overexpression of GLI1 and GLI2 has been considered a prognostic parameter for DFS and OS in HPV-negative HNSCC patients undergoing surgical resection and postoperative radiotherapy [ 69 ]. Our previous study revealed that some sets of OSCC with SHH expression showed HPV infection, but the relationship has not been statistically significant [ 57 ]. Likewise, Richtig et al did not reveal any correlations between GLI1, SMO, and p16 expression in the HNSCC cohort [ 68 ].…”

High expression of MARVELD3 as a potential prognostic biomarker for oral squamous cell carcinoma

“…At present, the main treatment methods for OSCC are mainly surgery, chemotherapy, and radiotherapy. The major causes of high mortality are high tumor invasion, lymph node involvement, poor response to therapy, and early local recurrence ( Cierpikowski et al, 2021 ). To be able to effectively improve the survival rate and improve prognosis in patients with OSCC, there is an urgent need to look for a potential biomarker.…”