Notch1-Jagged1 Signaling Pathway in Oral Squamous Cell Carcinoma: Relation to Tumor Recurrence and Patient Survival

Abstract

BACKGROUND: Dysregulated Jagged1/Notch1 signaling has been implicated in a variety of carcinomas, but little is known about the expression and possible role of Jagged1 and Notch1 in patients with oral squamous cell carcinoma (OSCC). AIM: We set out to examine the clinical significance of Notch1 and Jagged1 expression in OSCC. METHODS: Specimens were obtained from 44 patients who underwent surgical resection of primary OSCC. Immunostaining was done for Notch1 and Jagged1. The utilized markers’ expressions were analyzed in respect to 3 years overall survival (OS) and disease-free survival (DFS). RESULTS: Poor prognosis was significantly associated with high Notch1 expression, high Jagged1 expression, advanced TNM clinical stage (III and IV), presence of distant metastasis, presence of nodal involvement, large-sized tumors (≥4 cm), presence of lymphovascular invasion, higher grade carcinomas, high Notch1 and Jagged1 coexpression, and carcinomas aroused from tongue and palate. Notch1, Jagged1, histologic grade, and tumor site were the independent predictors of DFS, while Jagged1 expression, histologic grade, and tumor site were the independent predictors of 3 years OS. CONCLUSION: Our findings imply that either high levels of Notch1 or Jagged1 expression, or combined combination of both are related with poor prognostic outcomes.

Role of Mutation of NOTCH1 gene in development of oral squamous cell carcinoma: a narrative review

“…19 NOTCH1 protein are heterodynamic proteins. 21 There are three domains of NOTCH1 gene receptor; extracellular, transmemberane and intracytoplasmic. The extracellular domain is responsible for ligand binding, while the intracytoplasmic domain facilitates signal transduction.…”

Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges

“…Recently, it was reported that a STAT3-activated long non-coding RNA, hepatocyte nuclear factor 1 homeobox A antisense RNA 1, promoted tumorigenesis by activating the Notch pathway in OSCC cells[ 67 ]. Further, high expression of NOTCH1 and JAG1 have been shown to be predictors of poor OS as well as DFS in oral carcinoma patients[ 68 ]. The notch signaling pathway and its role in TSCC is shown in (Figure 3 ).…”