Identification of proteins implicated in the development of pancreatic cancer-associated diabetes mellitus by iTRAQ-based quantitative proteomics.

Studies have revealed that pancreatic cancer (PC) may lead to diabetes mellitus (DM). We aimed to identify the proteins implicated in the development of PC-associated DM in PC tissues with DM. We used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry to compare protein expression in PC tissues with DM with that in PC tissues without DM and in adjacent nontumor tissues with or without DM. A total of 80 surgically resected fresh tissues from 40 PC patients were included to identify differential protein expression. Western blotting and immunohistochemistry were then applied to evaluate the differential expression of selected proteins. A total of 1611 proteins were repeatedly identified and quantified by performing the iTRAQ-based experiments twice. Of these, 23 proteins were differentially expressed according to our defined criteria (12 upregulated and 11 downregulated). The S100 calcium binding protein A9 and aldehyde dehydrogenase 2 family were selected to validate the proteomic results by western blotting and immunohistochemistry. The identification of key proteins implicated in the development of PC-associated DM could serve as a foundation to better understand and further explore the etiology and pathogenesis of PC-associated DM. BIOLOGICAL SIGNIFICANCE: The identification of key proteins implicated in the development of PC-associated DM could serve as a foundation to better understand and further explore the etiology and pathogenesis of PC-associated DM.