Aberrant Signal Transduction and DNA Repair Pathways in Primary Lung Cancer Detected by Protein Profiling and their Association with Clinical Parameters

Abstract

Background: Because cell signaling and cell metabolic pathways are executed through proteins, characterizing protein signatures in tumor tissues is required to identify key nodes in signaling networks whose alteration is associated with malignancy. This study aimed to determine protein signatures in primary lung cancer tissues. Methods and Findings: Case-matched normal and tumor samples from 101 lung cancer patients, most of them with non-small cell lung cancer, were analyzed with reverse-phase protein array assay for 127 proteins and/or protein phosphorylation sites. Differences in signal intensities between normal and tumor tissues and their association with clinical parameters were analyzed with analysis of variance, some of them were further validated by Western blot and/or immunohistochemical analyses. We found that 18 molecules were significantly different (p<0.05) by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction, or lipid metabolism or function as cell surface/matrix proteins. Significant differences were found for 16 and 13 of the 18 molecules, respectively, when squamous cell carcinoma and adenocarcinoma were analyzed separately. The levels of some of those proteins were significantly higher either in tumors of nonsmokers than in those of smokers, or in poorly differentiated tumors than in well or moderately differentiated tumors, or a particular histopathological type of tumors, such as in neuroendocrinal tumors. The levels of 6 molecules could be used to distinguish tumor from the normal with the accuracy of 87%, whereas levels in eight molecules could separate patients into groups with poor or better survival outcomes. Conclusions: Our results demonstrated that molecules involved in DNA repair, signal transductions, lipid metabolism and cell proliferation were drastically aberrant in primary lung cancer tissues. Some of the protein biomarkers could be useful for molecular diagnosis or for predicting clinical outcomes of lung cancer. Aberrant Signal Transduction and DNA Repair Pathways in Primary Lung Cancer Detected by Protein Profiling and their Association with Clinical Parameters Yong He1, Zhen Zhou1, Wayne L. Hofstetter1, Yanbin Zhou1, Wenxian Hu1, Apar Pataer1, Arlene M. Correa1, Yiling Lu2, Jing Wang3, Lixia Diao3, Ignacio I. Wistuba4, Jack A. Roth1, Stephen G. Swisher1, Bingliang Fang1 1Department of Thoracic and Cardiovascular Surgery, 2Department of Systems Biology, 3Department of Bioinformatics and Computation Biology, 4Department of Pathology, The University of Texas M. D. Anderson Cancer Center, USA doi:10.4172/2155-9929.1000075