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


CONCLUSIONS
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.
Yee
John
J
Division of Thoracic Surgery, Vancouver General Hospital, the University of British Columbia, Canada.
Sadar
Marianne D
MD
Sin
Don D
DD
Kuzyk
Michael
M
Xing
Li
L
Kondra
Jennifer
J
McWilliams
Annette
A
Man
S F Paul
SF
Lam
Stephen
S
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D010455:Peptides / Q000032:analysis* / Q000302:isolation & purification; D001620:beta-Thromboglobulin / Q000032:analysis
D015415:Biomarkers; C061615:PPBP protein, human; D010455:Peptides; D001620:beta-Thromboglobulin; C009862:connective tissue-activating peptide