Integrative proteomics and tissue microarray profiling indicate the association between overexpressed serum proteins and non-small cell lung cancer

PLoS One. 2012;7(12):e51748. doi: 10.1371/journal.pone.0051748. Epub 2012 Dec 19.

Abstract

Lung cancer is the leading cause of cancer deaths worldwide. Clinically, the treatment of non-small cell lung cancer (NSCLC) can be improved by the early detection and risk screening among population. To meet this need, here we describe the application of extensive peptide level fractionation coupled with label free quantitative proteomics for the discovery of potential serum biomarkers for lung cancer, and the usage of Tissue microarray analysis (TMA) and Multiple reaction monitoring (MRM) assays for the following up validations in the verification phase. Using these state-of-art, currently available clinical proteomic approaches, in the discovery phase we confidently identified 647 serum proteins, and 101 proteins showed a statistically significant association with NSCLC in our 18 discovery samples. This serum proteomic dataset allowed us to discern the differential patterns and abnormal biological processes in the lung cancer blood. Of these proteins, Alpha-1B-glycoprotein (A1BG) and Leucine-rich alpha-2-glycoprotein (LRG1), two plasma glycoproteins with previously unknown function were selected as examples for which TMA and MRM verification were performed in a large sample set consisting about 100 patients. We revealed that A1BG and LRG1 were overexpressed in both the blood level and tumor sections, which can be referred to separate lung cancer patients from healthy cases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Blood Proteins / metabolism*
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Case-Control Studies
  • Chromatography, Liquid
  • Glycoproteins / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Lung Neoplasms / metabolism*
  • Proteomics*
  • Tandem Mass Spectrometry
  • Tissue Array Analysis

Substances

  • A1BG protein, human
  • Biomarkers, Tumor
  • Blood Proteins
  • Glycoproteins
  • Immunoglobulins
  • LRG1 protein, human

Grant support

This project was supported by grants from the Ministry of Science and Technology (2010CB912100, 2011CB910200), National Natural Science Foundation of China (91029301, 30821065, 81101760, 81172218, 81101761), Science and Technology Commission of Shanghai Municipality (09JC1416302), Chinese Academy of Science Project (KSCX2-YW-R-106, KSCX1-YW-02), Fudan University (09FQ78) and Fudan University Cancer Hospital (YJ200804, YJ200701). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.