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Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer.

ABSTRACT: There is a critical need for improvements in the noninvasive diagnosis of lung cancer. We hypothesized that matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) analysis of the most abundant peptides in the serum may distinguish lung cancer cases from matched controls.We used MALDI MS to analyze unfractionated serum from a total of 288 cases and matched controls split into training (n = 182) and test sets (n = 106). We used a training-testing paradigm with application of the model profile defined in a training set to a blinded test cohort.Reproducibility and lack of analytical bias was confirmed in quality-control studies. A serum proteomic signature of seven features in the training set reached an overall accuracy of 78%, a sensitivity of 67.4%, and a specificity of 88.9%. In the blinded test set, this signature reached an overall accuracy of 72.6 %, a sensitivity of 58%, and a specificity of 85.7%. The serum signature was associated with the diagnosis of lung cancer independently of gender, smoking status, smoking pack-years, and C-reactive protein levels. From this signature, we identified three discriminatory features as members of a cluster of truncated forms of serum amyloid A.We found a serum proteomic profile that discriminates lung cancer from matched controls. Proteomic analysis of unfractionated serum may have a role in the noninvasive diagnosis of lung cancer and will require methodological refinements and prospective validation to achieve clinical utility.

SUBMITTER: Yildiz PB

PROVIDER: S-EPMC4220686 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer.

Yildiz Pinar B PB Shyr Yu Y Rahman Jamshedur S M JS Wardwell Noel R NR Zimmerman Lisa J LJ Shakhtour Bashar B Gray William H WH Chen Shuo S Li Ming M Roder Heinrich H Liebler Daniel C DC Bigbee William L WL Siegfried Jill M JM Weissfeld Joel L JL Gonzalez Adriana L AL Ninan Mathew M Johnson David H DH Carbone David P DP Caprioli Richard M RM Massion Pierre P PP

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20071001 10

<h4>Purpose</h4>There is a critical need for improvements in the noninvasive diagnosis of lung cancer. We hypothesized that matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) analysis of the most abundant peptides in the serum may distinguish lung cancer cases from matched controls.<h4>Patients and methods</h4>We used MALDI MS to analyze unfractionated serum from a total of 288 cases and matched controls split into training (n = 182) and test sets (n = 106). We used a train ...[more]

PMID: 17909350

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Project description:RationaleThe low molecular weight (LMW) proteins present in circulating body fluids, such as serum and plasma, hold biological significance as possible biomarkers. A major obstacle in mass spectrometry-based proteomics of serum is the presence of abundant high molecular weight proteins which mask the identification and quantitation of lower molecular weight proteins. Traditional methods involve the use of affinity resins to remove high molecular weight proteins, such as albumin and immunoglobulin G, with concomitant loss of lower molecular weight proteins. Considering the importance of depleting high molecular proteins, this paper compares an affinity resin, a gel-filter, and an acetonitrile (ACN) precipitation method to achieve successful removal of high molecular weight proteins and recovery of lower molecular weight proteins.MethodsSerum enrichment was carried out by multiple methods such as with the commercially available serum protein mini kit, ACN precipitation, and a gel filter method. Mass spectrometric runs were carried out on an AB SCIEX ESI QTOF 5600 mass spectrometer. Mass spectrometry analysis of the enriched serum obtained by ACN precipitation and gel filter method was performed for global proteome profiling. Quantitative mass spectrometry using isobaric tags for relative and absolute quantitation (iTRAQ) for ACN-precipitated enriched serum was also carried out.ResultsThe gel filter method, though allowing for the resolution and identification of LMW proteins, was better suited for global proteome analysis and not preferred for quantitative proteomic experiments. In contrast, enrichment by the ACN precipitation method allowed for the reproducible identification and quantitation of LMW proteins having molecular weight ≥4 kDa.ConclusionsUsing only chilled ACN and centrifugation, most of the highly abundant proteins were successfully removed from the serum, while recovering a significant portion of the LMW proteome. A more rapid protocol, which is compatible with iTRAQ labeling, to achieve improved results has been elucidated, thus allowing for better screening and identification of potential biomarkers.

Dataset Information

Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer.

Publications

Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer.

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