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

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Pinar B Yildiz, Yu Shyr, Jamshedur S M Rahman, Noel R Wardwell, Lisa J Zimmerman, Bashar Shakhtour, William H Gray, Shuo Chen, Ming Li, Heinrich Roder, Daniel C Liebler, William L Bigbee, Jill M Siegfried, Joel L Weissfeld, Adriana L Gonzalez, Mathew Ninan, David H Johnson, David P Carbone, Richard M Caprioli, Pierre P Massion
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 2 Issue 10 Pg. 893-901 (Oct 2007) ISSN: 1556-1380 [Electronic] United States
• PMID: 17909350 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Blood Proteins
• Neoplasm Proteins

Topics

• Adenocarcinoma (blood, pathology)
• Biomarkers, Tumor (blood)
• Blood Proteins (metabolism)
• Carcinoma, Large Cell (blood, pathology)
• Carcinoma, Non-Small-Cell Lung (blood, pathology)
• Carcinoma, Small Cell (blood, pathology)
• Case-Control Studies
• Chromatography, Liquid
• Cohort Studies
• Female
• Humans
• Lung Neoplasms (blood, pathology)
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)
• Neoplasm Staging
• Neoplasms, Squamous Cell (blood, pathology)
• Prognosis
• Proteomics
• Sensitivity and Specificity
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization