Gene expression profiling of peripheral blood leukocytes identifies potential novel biomarkers of chronic obstructive pulmonary disease in current and former smokers

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with associated systemic effects.

Objective: To use gene expression microarrays in peripheral blood leukocytes of current and former cigarette smokers to identify differences associated with COPD.

Materials and methods: Random forest modelling and a split-sample case–control approach were used to identify candidate predictors.

Results: We identified 1013 genes and one smoking exposure variable that differentiated current and former smokers with or without COPD. This predictor set was reduced to a nine-gene classifier (IL6R, CCR2, PPP2CB, RASSF2, WTAP, DNTTIP2, GDAP1, LIPE and RPL14).

Conclusion: These gene expression profiles represent potential biomarkers for COPD and may help increase mechanistic understanding of the disease.

Keywords::

• Cigarette smoking
• COPD
• gene expression
• microarray
• leukocytes
• random forest

Acknowledgements

The authors gratefully acknowledge the contributions to this study and manuscript by Michael S. Paul, PhD and Alex Lindell from LineaGen, Inc., Salt Lake City, Utah and George J. Patskan, PhD and Willie J McKinney, PhD from Altria Client Services. The authors also acknowledge the comments of reviewers (Priyadarshi Basu, PhD and Robert McKallip, PhD), the editorial assistance of Eileen Y. Ivasauskas of Accuwrit Inc., data management by Zaigang Liu and microarray processing by Yankai Jia, PhD

Declaration of interest

Financial support was provided by Philip Morris USA Inc. and LineaGen, Inc. J.S.E., M.J.S., E.L.M., B.K.Z. and A.R.J. were employed through Altria Client Services at the time of manuscript preparation. The other authors declare no other potential conflicts of interest. The authors alone are responsible for the content and writing of the paper.