Decreased cytoplasmic X-box binding protein-1 expression is associated with poor prognosis and overall survival in patients with oral squamous cell carcinoma.

Squamous cell carcinoma is the most common cancer of the oral cavity. In spite of advancements in surgical, chemoradiological and targeted therapies, these therapeutic strategies still have had little impact on survival rates. X-box binding protein-1 (XBP-1) is a potent transcription factor that is involved in the unfolded protein response (UPR) pathway, which itself is activated in response to endoplasmic reticulum stress as a method to restore cellular homeostasis. The role XBP-1 plays in oral squamous cell carcinoma (OSCC) has yet to be determined. In this study, we used molecular and immunohistochemical analyses to investigate the role of XBP-1 protein playing in the OSCC carcinogenesis. We used immunohistochemical analyses to investigate XBP-1 expression in 255 OSCC tissue specimens, as well as migration and invasion assays with XBP-1 siRNA transfection of oral cancer cell lines to confirm its role in OSCC. The XBP-1 immunostaining was dichotomized as low-level expression and high-level expression. We found that low-level cytoplasmic XBP-1expression was significantly correlated with larger tumor size (p=0.047), more advanced clinical stage (p<0.0001), lymph node metastasis (p=0.002), and shorter overall survival (p=0.011). Kaplan-Meier survival curves showed that low-level cytoplasmic XBP-1 expression was significantly correlated with shorter overall survival (p=0.031). The univariate Cox regression analysis revealed that cytoplasmic XBP-1 expression was a prognostic factor for overall survival of patients with OSCC. We also found that inhibition of XBP-1 promoted OSCC cell migration and invasion. Our results suggest that XBP-1 expression may play an essential role in the pathogenesis of OSCC and that targeting XBP-1 may be a sound therapeutic strategy.