SLC5A8 Nuclear Translocation and Loss of Expression are Associated With Poor Outcome in Pancreatic Ductal Adenocarcinoma

Objectives: This study aimed to assess the role of SLC5A8 expression in the survival of pancreatic cancer. Methods: We determined SLC5A8 expression in pancreatic ductal adenocarcinoma and adjacent non-neoplastic pancreas (NNP) obtained from 110 patients who underwent pancreatectomy. Formalin-fixed paraffin-embedded core sections in a tissue microarray were immunostained using polyclonal anti-SLC5A8 antibody, and a semiquantitative measure of SLC5A8 expression was determined. Results: SLC5A8 expression was low in 56% (62/110) of pancreatic cancers as compared to NNP that had low expression in only 9% (10/107) of specimens (P < 0.0001). All cells expressing SLC5A8 did so in the cytoplasm, whether they are neoplastic or not. Nuclear expression of SLC5A8 occurred in 38% (42/110) of cancers, but it was uncommon in NNP (7%, 8/107) (P < 0.0001). Kaplan-Meier estimates showed that survival in patients whose cancers had low SLC5A8 expression, and/or nuclear expression, was significantly worse than in patients whose cancers had none of these abnormalities (P = 0.02). For the 88 patients whose cancers had abnormal SLC5A8 expression, median survival was 1.4 years, as compared to 3.9 years in patients whose cancers both expressed high levels of SLC5A8 and lacked nuclear expression. Conclusions: SLC5A8 nuclear translocation and loss of expression are associated with poor outcome in pancreatic ductal adenocarcinoma.