Background: Regenerating gene (REG) family is composed of antiapoptotic factors and growth factors that affect

epithelial cells within the digestive system. Regenerating gene-I has been studied in different cancers. However, it

has never been studied in head and neck cancer. We investigated the expression of REG-I in head and neck SCC

and its relevance to patient survival rates.

 Methods: Untreated biopsy specimens of 60 patients with stage IV head and neck SCC were collected, and the

expression of REG-I was evaluated using immunohistochemistry. The association between REG-I expression and

clinico-pathological features or survival status of the patients was assessed by Chi-square test, Fisher’s exact test and

Kaplan-Meier method. Cox proportional hazard model was used to identify the independent prognostic factors.

 Results: Incidence of lymphatic permeation, vascular invasion and pathological lymph nodes was significantly

higher in REG-I negative group (p = 0.008, 0.030 and 0.015, respectively). Overall and cancer-free survival rates were

significantly higher in REG-I positive group (p = 0.000434 and 1.0847E-8, respectively). Univariate analysis showed

that REG-I was an independent prognostic factor for predicting long-term overall survival (p = 0.002), and multivariate

analysis showed that REG-I and lymphatic permeation were independent prognostic factors for predicting long-term

disease-free survival (p = 0.001 and 0.022, respectively).

 Conclusion: Our results showed for the first time that, REG-I is expressed in head and neck SCC. REG-I expression is

associated with a longer survival status. We conclude that, REG-I might be a prognostic marker in head and neck SSC

and should be further investigated.