Background: Pancreatic cancer (PC)-associated diabetes is supposed to be consequent to diabetogenic effects of one or more tumour products. Patients and Methods: To analyze by MALDI-TOF analysis the peptide composition of: (1) conditioned media (CM) from 3 pancreatic cancer cell lines and (2) portal sera from 11 patients with PC with or without diabetes mellitus. PC cell CM were obtained from MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. Portal sera from patients with PC (7 with and 4 without diabetes) were collected at surgery by venipucture of the portal vein. Diabetes mellitus was diagnosed on the basis of fasting plasma glucose above 126 mg/dL or by post prandial glucose above 200 mg/dL. Results: In PC cell CM a total of 75 peptides were identified: of them 25 were common to non conditioned medium, while those at m/z 1680, 1856, 2030, 2309, 2483, 2623, 4182, 4334 and 4808 were only present in CM, probably representing tumour specific products. In patients’ portal sera we identified 173 protein/peptides with m/z ranging from 1098 to 150079. Among these only one was correlated with diabetes mellitus: that at m/z 5005, being found in 5/7 (71.4%) diabetic and in none of the non diabetic subjects (Fisher’s exact test: p 0.05). Interestingly, some peptides were negatively associated with the presence of diabetes mellitus: those at m/z 2554, 3285, 5020, 11748, 12636, 16011. In patients without the protein at m/z 11748 fasting plasma glucose levels resulted significantly (Wilcoxon W 10, p 0.05) higher than in those presenting this peptide in portal sera. Conclusions: MALDI-TOF analysis allowed us the detection of a large number of protein/peptides in complex mixtures as sera. With this method we identified a peptide at m/z of 5005 significantly correlated with the presence of PC-associated diabetes. The negative association found between PC-associated diabetes and some peptides, suggests that diabetes mellitus might be consequent not only to the diabetogenic effects of new tumor product(s), but also to the lacking production of some anti-diabetogenic substances.
Identification of pro- and anti-diabetogenic peptide(s) in portal sera of patients with pancreatic cancer
VALERIO, ANNA CANDIDA;BASSO, DANIELA;FOGAR, PAOLA;GRECO, ELIANA;ZAMBON, CARLO-FEDERICO;PEDRAZZOLI, SERGIO;PLEBANI, MARIO
2004
Abstract
Background: Pancreatic cancer (PC)-associated diabetes is supposed to be consequent to diabetogenic effects of one or more tumour products. Patients and Methods: To analyze by MALDI-TOF analysis the peptide composition of: (1) conditioned media (CM) from 3 pancreatic cancer cell lines and (2) portal sera from 11 patients with PC with or without diabetes mellitus. PC cell CM were obtained from MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. Portal sera from patients with PC (7 with and 4 without diabetes) were collected at surgery by venipucture of the portal vein. Diabetes mellitus was diagnosed on the basis of fasting plasma glucose above 126 mg/dL or by post prandial glucose above 200 mg/dL. Results: In PC cell CM a total of 75 peptides were identified: of them 25 were common to non conditioned medium, while those at m/z 1680, 1856, 2030, 2309, 2483, 2623, 4182, 4334 and 4808 were only present in CM, probably representing tumour specific products. In patients’ portal sera we identified 173 protein/peptides with m/z ranging from 1098 to 150079. Among these only one was correlated with diabetes mellitus: that at m/z 5005, being found in 5/7 (71.4%) diabetic and in none of the non diabetic subjects (Fisher’s exact test: p 0.05). Interestingly, some peptides were negatively associated with the presence of diabetes mellitus: those at m/z 2554, 3285, 5020, 11748, 12636, 16011. In patients without the protein at m/z 11748 fasting plasma glucose levels resulted significantly (Wilcoxon W 10, p 0.05) higher than in those presenting this peptide in portal sera. Conclusions: MALDI-TOF analysis allowed us the detection of a large number of protein/peptides in complex mixtures as sera. With this method we identified a peptide at m/z of 5005 significantly correlated with the presence of PC-associated diabetes. The negative association found between PC-associated diabetes and some peptides, suggests that diabetes mellitus might be consequent not only to the diabetogenic effects of new tumor product(s), but also to the lacking production of some anti-diabetogenic substances.
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