Pancreatic adenocarcinoma up-regulated factor has oncogenic functions in oral squamous cell carcinoma

Aims: Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel secretory protein which promotes tumour progression, metastasis and poor prognosis in pancreatic, cervical and colorectal carcinoma. It is also associated with gemcitabine resistance in pancreatic cancer cells. However, the expression and function of PAUF in oral squamous cell carcinoma (OSCC) remain unknown. Methods and results: We performed an immunohistochemical analysis of PAUF in 222 clinicopathologically characterized cases of OSCC. We also investigated the growth, invasion, apoptosis induction and cisplatin resistance of OSCC cells under PAUF knockdown treatment. PAUF was localized in normal salivary glands. In OSCC, immunostaining for PAUF was found in 52 of 222 patients (23.4%), and correlated with nodal metastasis (P < 0.0001) and poor prognosis (P < 0.0001). Multivariate analysis using the Cox proportional hazards model identified that PAUF expression was an independent predictor of disease-free survival in OSCC (P < 0.0001). The down-regulation of PAUF in OSCC cells suppressed cell growth and invasion and induced apoptosis and cisplatin sensitivity. Conclusions: Our results suggest that PAUF has tumour-promoting functions in OSCC. It may thus be a useful diagnostic and therapeutic marker for OSCC.