Identification of apolipoprotein C-1 as a novel prognostic serum marker of pancreatic cancer and its expression in cancer cells

A55

Pancreatic cancer still remains one of the most lethal diseases with increasing incidence and establishment of new therapy is needed. The purpose of this study is to find novel serum factors involved in pancreatic cancer development, by protein profiling using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and ProteinChip analysis.For this purpose, we compared pre- and postoperative serum protein profiling obtained from patients with pancreatic cancer. Samples from twenty patients who underwent curative pancreatectomy were analyzed. Clusters of 85 peaks were differentially expressed in pre- and postoperative serum of pancreatic cancer patients, and proteins with 6630 Da and 6420 Da m/z peaks were candidates for pancreatic cancer-specific proteins as more abundantly expressed in preoperative serum than in postoperative serum (p< 0.002). Sequential amino acid analysis revealed the protein to be Apolipoprotein C-1 (ApoC-1), and it was confirmed the target protein as ApoC-1 by western blot analysis.The high level of ApoC-1 in preoperative serum significantly correlated with shorter disease-free (p< 0.001) and overall survival time (p< 0.005), and multivariate analysis also showed that ApoC-1 peak intensity level was an independent prognostic factor. This fact indicates the usefulness of ApoC-1 serum level as prognostic marker of pancreatic cancer. On the other hand, preoperative serum CA19-9 level, a widely used marker for pancreatic cancer, showed no correlation with disease-free and overall survival time in these twenty patients. This indicates that ApoC-1 is possible to be a better molecular marker for prediction of pancreatic cancer patients' prognosis than existing markers.Next, we showed that ApoC-1 was highly expressed in the pancreatic cancer cells themselves, but not in normal pancreatic ductal cells, a conclusion arrived based on the results of immunostaining, quantitative RT-PCR and Western blot. Interestingly, high mRNA level of ApoC-1 in pancreatic cancer tissues correlated with poor prognosis of patients in another different group, as high serum peak intensity level of this protein did.In conclusion, we found that serum ApoC-1 expression, which is derived from cancer cells, can be used as a marker to predict the prognosis of pancreatic cancer patients. Our results demonstrate that proteomic analysis in cancer research is fruitful not only in terms of diagnostic marker discovery, but in identifying prognostic factors and leads to discovery the therapeutic targets of cancer.