Persistent alterations of gene expression profiling of human peripheral blood mononuclear cells from smokers
Daniel Y. Weng
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Search for more papers by this authorJinguo Chen
Center for Human Immunology, National Institute of Health, Bethesda, Maryland
Search for more papers by this authorCenny Taslim
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Search for more papers by this authorPing-Ching Hsu
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Search for more papers by this authorCatalin Marian
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
University of Medicine and Pharmacy, Timisoara, Romania
Search for more papers by this authorSean P. David
Department of Medicine, Stanford University School of Medicine, Stanford, California
Search for more papers by this authorChristopher A. Loffredo
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia
Search for more papers by this authorCorresponding Author
Peter G. Shields
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Correspondence to: Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, 460 W. 10th Avenue, 9th Floor, Suite D920, Columbus, OH 43210-1240.
Search for more papers by this authorDaniel Y. Weng
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Search for more papers by this authorJinguo Chen
Center for Human Immunology, National Institute of Health, Bethesda, Maryland
Search for more papers by this authorCenny Taslim
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Search for more papers by this authorPing-Ching Hsu
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Search for more papers by this authorCatalin Marian
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
University of Medicine and Pharmacy, Timisoara, Romania
Search for more papers by this authorSean P. David
Department of Medicine, Stanford University School of Medicine, Stanford, California
Search for more papers by this authorChristopher A. Loffredo
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia
Search for more papers by this authorCorresponding Author
Peter G. Shields
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Correspondence to: Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, 460 W. 10th Avenue, 9th Floor, Suite D920, Columbus, OH 43210-1240.
Search for more papers by this authorAbstract
The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke, effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacco products. We assessed the effects of smoking on the gene expression using human cell cultures and blood from a cross-sectional study. We profiled global transcriptional changes in cultured smokers’ peripheral blood mononuclear cells (PBMCs) treated with cigarette smoke condensate (CSC) in vitro (n = 7) and from well-characterized smokers’ blood (n = 36). ANOVA with adjustment for covariates and Pearson correlation were used for statistical analysis in this study. CSC in vitro altered the expression of 1 178 genes (177 genes with > 1.5-fold-change) at P < 0.05. In vivo, PBMCs of heavy and light smokers differed for 614 genes (29 with > 1.5-fold-change) at P < 0.05 (309 remaining significant after adjustment for age, race, and gender). Forty-one genes were persistently altered both in vitro and in vivo, 22 having the same expression pattern reported for non-small cell lung cancer. Our data provides evidence that persistent alterations of gene expression in vitro and in vivo may relate to carcinogenic effects of cigarette smoke, and the identified genes may serve as potential biomarkers for cancer. The use of an in vitro model to corroborate results from human studies provides a novel way to understand human exposure and effect. © 2015 Wiley Periodicals, Inc.
Supporting Information
Additional supporting information may be found in the online version of this article at the publisher's web-site.
| Filename | Description |
|---|---|
| mc22385-sup-0001-SuppData-S1.pdf701.6 KB |
Supplementary Table S1. Primer sequences used in RT-qPCR. Supplementary Table S2. Up and down regulated genes following CSC stimulation of cultured PBMCs. Supplementary Table S3. Selected gene ontology GO categories significantly affected by CSC stimulation. Supplementary Table S4. Up and down regulated genes in PBMCs of heavy smokers compared with light smokers. Supplementary Table S5. Selected gene ontology GO categories significantly affected by heavy smokers compared with light smokers. Supplementary Table S6. Significant genes adjusted for age, race, and gender among smokers. Supplementary Table S7. The significant IPA canonical pathways assignment for the set of CSC-stimulated genes. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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