Comparison Of Proteomic Profiles In Human Plasma Of Smokers And Nonsmokers Using The Itraq Approach

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Lung cancer is a potentially preventable disease because it is strongly related to tobacco smoke. Although there have been great strides taken to inform the population of the severity of the risks associated with smoking, there are currently 43.4 million Americans that smoke and 1.3 billion smokers worldwide. Therefore, it is important to develop biomarkers that can identify individual smokers and ex-smokers who are at especially high risk for lung cancer. Relative changes that take place in the human plasma proteome as a result of smoking may be playing an important role in the etiology of lung cancer. Thus, in this study we used a proteomic approach utilizing isobaric Tag for Relative and Absolute Quantitation (iTRAQ) to compare the plasma protein expression levels between healthy smokers and non-smokers. With this multi-plex non-gel based technique, up to 8 samples can be simultaneously labeled with isobaric tagging reagents, 113-119 and 121, for quantitation and identification by mass spectrometry. Plasma samples from seven white male smokers and seven white male non-smokers were distributed into two 8-plex iTRAQ sets. The 113 label in each set was used to label a pool consisting of each sample in the study in order to compare between the two 8-plex sets. Plasma from each subject was depleted of the 14 most abundant plasma proteins using an immunoaffinity column to search for lower abundant proteins. Based on our results, we identified 18 significant (p<0.05) differentially expressed proteins between smokers and non-smokers. The proteins that were down-regulated in smokers include sex hormone-binding globulin (SHBG), inter-α (globulin) inhibitor H3 (HC3), and vitronectin. The proteins that were up-regulated in smokers include the complement component 8, α, β and γ polypeptides, gelsolin, and mannose-binding protein C (MBP-C). Among those identified, SHBG, HC3, and gelsolin protein have been previously identified in smokers and have been suggested to be candidate markers for lung cancer. The results of this study show that cigarette smoking can influence the relative expression profile of plasma proteins. However, the relationship of these proteins to the development of lung cancer needs to be determined so that they can be further developed as biomarkers of disease risk. Support: NCI PO1 70972 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4572.