Annexin II Overexpression Predicts Rapid Recurrence after Surgery in Pancreatic Cancer Patients Undergoing Gemcitabine-Adjuvant Chemotherapy

Abstract

Gemcitabine has been shown to exhibit significant clinical activity against pancreatic cancer and has become a first-line chemotherapeutic for this disease in recent years. However, there are still many patients who do not respond to this treatment and it is expected to improve the clinical outcome if we can develop a method to predict the efficacy of gemcitabine before treatment. The purpose of this study was to determine novel factors that make pancreatic cancer resistant to gemcitabine. Using the high-resolution proteomic approach, agarose two-dimensional gel electrophoresis, we compared protein profiling of a gemcitabine-resistant pancreatic cancer cell line with its wild-type. We identified Annexin II as an up-regulated protein in the gemcitabine-resistant pancreatic cancer cell line. Immunohistochemistry demonstrated that Annexin II was mainly expressed at the cell surface of pancreatic cancer cells. Interestingly, Annexin II overexpression in cancer cells was significantly associated with rapid recurrence after gemcitabine adjuvant chemotherapy in postoperative patients (P = .0078), and its staining was also an independent prognostic indicator of recurrence in pancreatic cancer patients who underwent adjuvant gemcitabine treatment after curative surgery on multivariate analysis (P = .0047). In addition, inhibition of Annexin II expression by siRNA in pancreatic cancer cell lines increased the cytotoxic efficacy of gemcitabine. These results indicate that Annexin II overexpression may induce gemcitabine resistance in pancreatic cancer resulting in rapid recurrence. Analysis of Annexin II expression in cancer tissues may predict the clinical outcome of gemcitabine treatment, leading to the development of a new method for tailor-made treatment for this disease.