title: Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility.
abstract: BACKGROUND
  It is well known that many malignancies, including pancreatic cancer (PC), possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility.
  
  
  RESULTS
  PBMC samples from 26 PC patients and 33 matched healthy controls were analyzed by whole genome cDNA microarray. Three hundred eighty-three genes were found to be significantly different between PC and healthy controls, with 65 having at least a 1.5 fold change in expression. Pathway analysis revealed that many of these genes fell into pathways responsible for hematopoietic differentiation, cytokine signaling, and natural killer (NK) cell and CD8+ T-cell cytotoxic response. Unsupervised hierarchical clustering analysis identified an eight-gene predictor set, consisting of SSBP2, Ube2b-rs1, CA5B, F5, TBC1D8, ANXA3, ARG1, and ADAMTS20, that could distinguish PC patients from healthy controls with an accuracy of 79% in a blinded subset of samples from treatment naïve patients, giving a sensitivity of 83% and a specificity of 75%.
  
  
  CONCLUSIONS
  In summary, we report the first in-depth comparison of global gene expression profiles of PBMCs between PC patients and healthy controls. We have also identified a gene predictor set that can potentially be developed further for use in diagnostic algorithms in PC. Future directions of this research should include analysis of PBMC expression profiles in patients with chronic pancreatitis as well as increasing the number of early-stage patients to assess the utility of PBMCs in the early diagnosis of PC.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center Omaha, Omaha, Nebraska, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Baine
authors.forename: Subhankar
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.forename: Kavita
authors.initials: K
authors.lastname: Mallya
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Sasson
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000235:genetics*; D059467:Transcriptome