Location of Repository

A Comprehensive Peptidome Profiling Technology for the Identification of Early Detection Biomarkers for Lung Adenocarcinoma

By Koji Ueda, Naomi Saichi, Sachiko Takami, Daechun Kang, Atsuhiko Toyama, Yataro Daigo, Nobuhisa Ishikawa, Nobuoki Kohno, Kenji Tamura, Taro Shuin, Masato Nakayama, Taka-Aki Sato, Yusuke Nakamura and Hidewaki Nakagawa


The mass spectrometry-based peptidomics approaches have proven its usefulness in several areas such as the discovery of physiologically active peptides or biomarker candidates derived from various biological fluids including blood and cerebrospinal fluid. However, to identify biomarkers that are reproducible and clinically applicable, development of a novel technology, which enables rapid, sensitive, and quantitative analysis using hundreds of clinical specimens, has been eagerly awaited. Here we report an integrative peptidomic approach for identification of lung cancer-specific serum peptide biomarkers. It is based on the one-step effective enrichment of peptidome fractions (molecular weight of 1,000–5,000) with size exclusion chromatography in combination with the precise label-free quantification analysis of nano-LC/MS/MS data set using Expressionist proteome server platform. We applied this method to 92 serum samples well-managed with our SOP (standard operating procedure) (30 healthy controls and 62 lung adenocarcinoma patients), and quantitatively assessed the detected 3,537 peptide signals. Among them, 118 peptides showed significantly altered serum levels between the control and lung cancer groups (p<0.01 and fold change >5.0). Subsequently we identified peptide sequences by MS/MS analysis and further assessed the reproducibility of Expressionist-based quantification results and their diagnostic powers by MRM-based relative-quantification analysis for 96 independently prepared serum samples and found that APOA4 273–283, FIBA 5–16, and LBN 306–313 should be clinically useful biomarkers for both early detection and tumor staging of lung cancer. Our peptidome profiling technology can provide simple, high-throughput, and reliable quantification of a large number of clinical samples, which is applicable for diverse peptidome-targeting biomarker discoveries using any types of biological specimens

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3075260
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (2009). A human proteome detection and quantitation project.
    2. (2010). A magnetic beadbased serum proteomic fingerprinting method for parallel analytical analysis and micropreparative purification.
    3. (2002). A new gene, EVC2, is mutated in Ellis-van Creveld syndrome.
    4. (2000). A new member of acid-sensing ion channels from pituitary gland.
    5. (2010). A peptidomics strategy for discovering endogenous bioactive peptides.
    6. (2009). Afamin and apolipoprotein A-IV: novel protein markers for ovarian cancer.
    7. (2006). Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha.
    8. (2008). Biomarkers for the lung cancer diagnosis and their advances in proteomics.
    9. Blobel CP (2007) In search of partners: linking extracellular proteases to substrates.
    10. (2010). Blood peptidomedegradome profile of breast cancer.
    11. (2008). Cysteine cathepsin proteases as pharmacological targets in cancer.
    12. (2010). Development of serum glycoproteomic profiling technique; simultaneous identification of glycosylation sites and site-specific quantification of glycan structure changes.
    13. (2010). Different expression of fibrinopeptide A and related fragments in serum of type 1 diabetic patients with nephropathy.
    14. (2010). Differential expression of proteomics models of colorectal cancer, colorectal benign disease and healthy controls.
    15. (2007). Emerging roles of proteases in tumour suppression.
    16. (2000). Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men.
    17. (2001). Global cancer statistics in the year
    18. (2006). Identification and confirmation of increased fibrinopeptide a serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry.
    19. (2009). Limitations in SELDITOF MS whole serum proteomic profiling with IMAC surface to specifically detect colorectal cancer.
    20. (2009). Lung cancer in never smokers: clinical epidemiology and environmental risk factors.
    21. (2009). MALDI profiling of human lung cancer subtypes.
    22. (2009). MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of systemic lupus erythematosus. Rheumatology (Oxford)
    23. (2009). Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.
    24. (2009). Mining novel biomarkers for prognosis of gastric cancer with serum proteomics.
    25. (2009). Monitoring peptidase activities in complex proteomes by MALDI-TOF mass spectrometry.
    26. (1988). Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer.
    27. (2002). New functions for the matrix metalloproteinases in cancer progression.
    28. (2002). Prognostic factors in non-small cell lung cancer: a decade of progress.
    29. (2008). Proteases: multifunctional enzymes in life and disease.
    30. (2007). Proteomic approaches for serum biomarker discovery in cancer.
    31. (2006). Survival of patients with stage I lung cancer detected on CT screening.
    32. (2009). Targeted proteomic strategy for clinical biomarker discovery.
    33. (2007). The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours.
    34. (2001). Tumor markers: should we or shouldn’t we?
    35. (2010). Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer.
    36. (2005). Upregulated expression of human neutrophil

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.