Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.

TitleConnective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.
Publication TypeJournal Article
Year of Publication2009
AuthorsYee, J, Sadar, MD, Sin, DD, Kuzyk, M, Xing, L, Kondra, J, McWilliams, A, Man, SFPaul, Lam, S
JournalJ Clin Oncol
Volume27
Issue17
Pagination2787-92
Date Published2009 Jun 10
ISSN1527-7755
KeywordsAged, Aged, 80 and over, beta-Thromboglobulin, Biological Markers, Early Detection of Cancer, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neutrophils, Peptides
Abstract

PURPOSE: There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background.

METHODS: Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer.

RESULTS: Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone.

CONCLUSION: We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.

DOI10.1200/JCO.2008.19.4233
Alternate JournalJ. Clin. Oncol.
PubMed ID19414677
PubMed Central IDPMC2698017
Grant List1P01-CA96964 / CA / NCI NIH HHS / United States
CA105304 / CA / NCI NIH HHS / United States
N01-CN-85188 / CN / NCI NIH HHS / United States
N01-HR-46002 / HR / NHLBI NIH HHS / United States
U01CA96109 / CA / NCI NIH HHS / United States