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Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility

Baine, MJ and Chakraborty, S and Smith, LM and Mallya, K and Sasson, AR and Brand, RE and Batra, SK (2011) Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility. PLoS ONE, 6 (2).

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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. Methods and Findings: 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. © 2011 Baine et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Baine, MJ
Chakraborty, S
Smith, LM
Mallya, K
Sasson, AR
Brand, REreb53@pitt.eduREB53
Batra, SK
Date: 25 February 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0017014
Refereed: Yes
MeSH Headings: Case-Control Studies; Female; Humans; Leukocytes, Mononuclear--metabolism; Male; Middle Aged; Pancreatic Neoplasms--diagnosis; Pancreatic Neoplasms--genetics; Pancreatic Neoplasms--pathology; Reproducibility of Results; Sensitivity and Specificity; Transcription, Genetic--genetics; Transcriptome
Other ID: NLM PMC3037404
PubMed Central ID: PMC3037404
PubMed ID: 21347333
Date Deposited: 07 Aug 2012 15:43
Last Modified: 27 Jan 2019 05:55
URI: http://d-scholarship.pitt.edu/id/eprint/13353

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