Protein Signature of Lung Cancer Tissues

Geoffrey S Baird,Nebojsa Janjic,Wei Xiong,Rossella Rota,Jeffrey J Walker,Michael R Mehan,Deborah Ayers,Sheri K Wilcox,Edward N Brody,Larry Gold,Rachel M Ostroff,Thale C Jarvis,Derek Thirstrup

doi:10.1371/journal.pone.0035157

Abstract

Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment.

Highlights

Progression from healthy state to disease is accompanied by changes in protein expression in affected tissues
Proteomic analysis of non small-cell lung cancer (NSCLC) surgical resections In this report, we performed large-scale protein expression analysis of homogenized lung tissue samples from surgical resections obtained from eight non-small cell lung cancer (NSCLC) patients
Fibrinogen is the soluble precursor of fibrin, which is converted by thrombin during coagulation

Summary

Introduction

Progression from healthy state to disease is accompanied by changes in protein expression in affected tissues. Comparative interrogation of the human proteome in healthy and diseased tissues can offer insights into the biology of disease and lead to discovery of new biomarkers for diagnostics, new targets for therapeutic intervention, and identification of patients most likely to benefit from targeted treatment. New diagnostics for early detection of lung cancer are urgently needed. Lung cancer is the leading cause of cancer deaths, largely because 84% of cases are diagnosed at an advanced stage, with a five-year survival rate of less than 15% [1,2,3]. Patients diagnosed with NSCLC at an early stage and treated surgically to remove their tumors experience an 86% five-year survival [1,2]

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