Serum biomarkers of pancreatic cancer (PC) and pancreatic cancer derived diabetes mellitus (DM).

Objective To verify whether discontinuous SDS-PAGE, performed in the conditions which allowed the isolation of NT-S100A8 from PC tissues, can identify potential serum markers of PC and PC induced DM. Methods We collected sera from 42 PC patients (17 with and 25 without DM) and from 11 healthy controls (C). Results In the low MW range (15,000-1,000 Da), nine protein bands were identified and numbered 1 to 9 from heaviest to lightest. Only band number 2 (14,200 Da approximately) was correlated with PC diagnosis, being present in 10/11 C and absent in 37/42 cancer cases (chi squared=26.8, P<0.001). Two bands, 4 and 9, MW 10,000 and 1,000 Da respectively, correlated with each other (chi squared=4.8, P<0.05). In PC, the absence of both bands correlated with the presence of DM (chi squared=8.6, P<0.01 for band 4 and chi squared=6.6, P<0.05 for band 9) and was significantly associated with higher fasting plasma glucose levels (P<0.05 for band 4 and P<0.01 for band 9). The absence of band 9 was also significantly associated with HbA1c (P<0.05) and with glucose/C-peptide ratio (P<0.05). To characterize the protein inversely correlated with PC diagnosis, we performed a MALDI-TOF analysis of the tryptic in-gel digestion of band 2. The identified peaks were analyzed by Mascot Peptide Mass Fingerprint and showed a high homology with human hemoglobin subunit b (score 76, P<0.05) Conclusion SDS-PAGE analysis of the low MW serum proteins allowed the detection of peptides correlated with PC derived DM and the identification of free beta globin as a potential PC serum marker.