Higher levels of the anti-inflammatory protein CC10 are associated with improvement in bronchial dysplasia and sputum cytometric assessment in individuals at high risk for lung cancer.
OBJECTIVE
CC10, a 10-kDa anti-inflammatory protein secreted by bronchiolar Clara cells, is infrequently expressed in non-small cell lung cancer and its overexpression in non-small cell lung cancer cell lines results in a less malignant phenotype. Several lines of evidence have shown that bronchial dysplasia and sputum atypia are predictors of lung cancer. We investigated whether changes in CC10 expression correlate with regression of bronchial dysplasia and/or improvement in sputum abnormalities as measured by image cytometry.


METHODS
High-risk smokers enrolled in a chemoprevention trial underwent serial bronchoscopies with biopsies and bronchoalveolar lavage (BAL) collection, sputum assessment by image cytometry, and blood collection. CC10 was measured by competitive ELISA in BAL and plasma. Logistic regression analyses were done to determine the associations between CC10 levels and the improvement in bronchial dysplasia and sputum cytometric assessment.


RESULTS
The net change in the BAL CC10 levels in subjects with improved bronchial lesions or improved sputum cytometry assessment was significantly higher than in those without improvement (P < 0.05). The odds ratio (95% confidence interval) associated with 1-unit increase in CC10 was 2.72 (1.31-5.64) for regression of dysplastic lesions and 2.94 (1.22-7.05) for improvement in sputum cytometry assessment after multivariate adjustment. Plasma CC10 was not significantly associated with either outcome.


CONCLUSIONS
Higher BAL CC10 levels are significantly correlated with regression of bronchial dysplasia and improvement in sputum cytometry assessment in smokers with high lung cancer risk. Whether CC10 levels can predict clinical outcomes among high-risk populations warrants further investigation.
Chen
Jiping
J
Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Lam
Stephen
S
Pilon
Aprile
A
McWilliams
Annette
A
Macaulay
Calum
C
Szabo
Eva
E
D000328:Adult; D000368:Aged; D001984:Bronchial Neoplasms / Q000378:metabolism* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D013183:Sputum / Q000166:cytology / Q000378:metabolism*; D014598:Uteroglobin / Q000378:metabolism*
C556389:SCGB1A1 protein, human; D014598:Uteroglobin