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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalJournal of Thoracic Oncology
Volume2
Issue number10
DOIs
StatePublished - Oct 2007

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Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Lung Neoplasms
Serum
Proteomics
Smoking
Serum Amyloid A Protein
Quality Control
C-Reactive Protein
Peptides

Keywords

  • Biomarker
  • Blood
  • Diagnosis
  • Mass spectrometry

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Yildiz, P. B., Shyr, Y., Rahman, J. S. M., Wardwell, N. R., Zimmerman, L. J., Shakhtour, B., ... Massion, P. P. (2007). Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer. Journal of Thoracic Oncology, 2(10), 893-901. https://doi.org/10.1097/JTO.0b013e31814b8be7

Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer. / Yildiz, Pinar B.; Shyr, Yu; Rahman, Jamshedur S M; Wardwell, Noel R.; Zimmerman, Lisa J.; Shakhtour, Bashar; Gray, William H.; Chen, Shuo; Li, Ming; Roder, Heinrich; Liebler, Daniel C.; Bigbee, William L.; Siegfried, Jill M.; Weissfeld, Joel L.; Gonzalez, Adriana L.; Ninan, Mathew; Johnson, David H.; Carbone, David P.; Caprioli, Richard M.; Massion, Pierre P.

In: Journal of Thoracic Oncology, Vol. 2, No. 10, 10.2007, p. 893-901.

Research output: Contribution to journalArticle

Yildiz, PB, Shyr, Y, Rahman, JSM, Wardwell, NR, Zimmerman, LJ, Shakhtour, B, Gray, WH, Chen, S, Li, M, Roder, H, Liebler, DC, Bigbee, WL, Siegfried, JM, Weissfeld, JL, Gonzalez, AL, Ninan, M, Johnson, DH, Carbone, DP, Caprioli, RM & Massion, PP 2007, 'Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer', Journal of Thoracic Oncology, vol. 2, no. 10, pp. 893-901. https://doi.org/10.1097/JTO.0b013e31814b8be7
Yildiz, Pinar B. ; Shyr, Yu ; Rahman, Jamshedur S M ; Wardwell, Noel R. ; Zimmerman, Lisa J. ; Shakhtour, Bashar ; Gray, William H. ; Chen, Shuo ; Li, Ming ; Roder, Heinrich ; Liebler, Daniel C. ; Bigbee, William L. ; Siegfried, Jill M. ; Weissfeld, Joel L. ; Gonzalez, Adriana L. ; Ninan, Mathew ; Johnson, David H. ; Carbone, David P. ; Caprioli, Richard M. ; Massion, Pierre P. / Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer. In: Journal of Thoracic Oncology. 2007 ; Vol. 2, No. 10. pp. 893-901.
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T1 - Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer

AU - Yildiz, Pinar B.

AU - Shyr, Yu

AU - Rahman, Jamshedur S M

AU - Wardwell, Noel R.

AU - Zimmerman, Lisa J.

AU - Shakhtour, Bashar

AU - Gray, William H.

AU - Chen, Shuo

AU - Li, Ming

AU - Roder, Heinrich

AU - Liebler, Daniel C.

AU - Bigbee, William L.

AU - Siegfried, Jill M.

AU - Weissfeld, Joel L.

AU - Gonzalez, Adriana L.

AU - Ninan, Mathew

AU - Johnson, David H.

AU - Carbone, David P.

AU - Caprioli, Richard M.

AU - Massion, Pierre P.

PY - 2007/10

Y1 - 2007/10

N2 - 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.

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KW - Biomarker

KW - Blood

KW - Diagnosis

KW - Mass spectrometry

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