A Comprehensive Proteome Analysis of Peripheral Blood Mononuclear Cells (PBMCs) to Identify Candidate Biomarkers of Pancreatic Cancer

Abstract

Background/Aim: Pancreatic cancer (PC) is currently the fourth leading cause of cancer-related mortality worldwide. Peripheral blood mononuclear cells (PBMCs) is a subpopulation of accessible and functional immune cells. Comparative analysis of the proteome of PBMCs can help us elucidate the mechanism of disease and find potential biomarkers for diagnosis. Materials and Methods: PBMCs were collected from healthy individuals, patients with benign diseases, and pancreatic cancer. iTRAQ-2DLC-MS/MS and SWATH methodologies were applied to make a comparative proteomics analysis of PBMCs. Results: A total of 3,357 proteins with a false discovery rate (FDR) <1% were identified, of which 114 proteins were found dysregulated in the PC group. An extensive SWATH library was constructed which showed a potential application for large scale clinical sample analysis. Conclusion: A PBMCs proteome with extensive protein representation was achieved, which will potentially allow the identification of novel biomarkers for PC. Pancreatic cancer (PC) is an aggressive malignancy, characterized by invasiveness, rapid progression and profound resistance to treatments (1-3). To date, there are no clinically validated screening methods for PC in the curative stage (4, 5). There is an urgent need for additional studies, applying modern technologies, on PC to increase our understanding of this disease, and improve the ability to diagnose PC in asymptomatic patients. In our previous work, surgically resected fresh PC tissues and adjacent non-tumor tissues were investigated and novel prognostic predictors of PC and PC-associated diabetes mellitus were discovered (6, 7). Given the asymptomatic nature of PC, a blood-based assay is preferred because it would be feasible and minimally invasive (8). Peripheral blood mononuclear cells (PBMCs), including monocytes, T-cells, B cells, and natural killer (NK) cells (9), play important roles in the function of the immune system and in monitoring immune-relevant events. They are readily accessible from routinely collected blood. Furthermore, it is known that the immune system is involved not only in the pathogenesis of autoimmune and infectious diseases, but also in cancer (10, 11), metabolic syndrome (12), atherosclerosis (13) and many other diseases (14). The PBMCs represent a biological sample which closely reflect the response of the body to pathogens and diseases like cancer. Therefore, they may allow for discovery of potentially pathology-relevant biomolecules of PC, such as DNA, RNA and proteins (15). Baine et al. reported an in-depth comparison of global gene expression profiles in PBMCs of PC patients and healthy controls, revealing that 383 genes were significantly different between PC and healthy controls (16). However, it is unknown whether these alterations have been transferred into the proteome of PBMCs in PC. Proteomic analysis provides large-scale determination of gene and cellular function at the protein level, so that it is quintessential to understanding health and disease of any organ ...

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“…Peripheral blood mononuclear cells (PBMCs) are immune cells that include lymphocytes and monocytes, and play a key role in the host immune system to fight against various abnormal conditions such as infection and carcinoma ( 6 ). Various studies have demonstrated that the gene expression level of PBMCs was significantly changed in patients with tumors and detection of changes in PBMCs may help to improve the diagnosis ( 7 , 8 ). Ciarloni et al ( 9 ) demonstrated the potential for developing a noninvasive and accurate inspection to identify patients at an average risk of colorectal cancer based on gene expression analysis of PBMCs segregated from patient blood samples.…”