Identification of specific pancreatic serum protein marker for early diagnosis by using ProteinChip technology

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We compared pre- and postoperative serum protein profiling obtained from pancreatic cancer patients who had curative pancreatectomy using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). The peak intensity levels of both 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum (p<0. 002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1). Furthermore, ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was detected in the culture medium of the pancreatic cancer cell line in vitro, which suggests that cancer cells secrete ApoC-1. The high level of ApoC-1 in preoperative serum significantly correlated with poor prognosis in the preoperative serum samples from an independent group of 69 pancreatic cancer patients who had surgical resection of cancer. We also performed the receiver-operator-characteristics (ROC) analysis between patients with survival time more and less than two years. The respective area under the ROC curve (AUC) was 0. 66 for ApoC-1 peak intensity and 0. 60 for CA19-9 level. These results indicated that serum ApoC-1 peak intensity had the better ability as a prognostic marker than serum CA19-9 level.Inhibition of ApoC-1 expression by siRNA suppressed cell proliferation and induced apoptosis of pancreatic cancer cells. The specific expression of ApoC-1 and its rote in preventing from spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target.