A CASE-COHORT STUDY OF AN EARLY BIOMARKER OF LUNG-CANCER IN A SCREENING COHORT OF YUNNAN TIN MINERS IN CHINA

We initiated the present study to evaluate the accuracy of a new epith elial biomarker of early lung cancer, We tested the hypothesis that ex pression of a tumor-associated antigen by exfoliated sputum epithelial cells has greater accuracy (sensitivity and specificity) for the dete ction of preclinical, localized lung cancer than do routine clinical d etection methods, Monoclonal antibody (MAb) 703D4 recognizes heterogen eous nuclear ribonuclear protein (hnRNP) A2/B1, We compared the accura cy of hnRNP up-regulation with cytology and radiographic screening for lung cancer detection in miners who were highly exposed to tobacco sm oke, radon, and arsenic in southwestern China, The results showed that MAb 703D4 detection of hnRNP expression by sputum epithelial cells ha d greater accuracy for the detection of lung cancer than did routine s creening methods, particularly for early (localized) disease, Among 57 cases and 76 noncases at the first screening, overall MAb detection o f hnRNP was more sensitive (74 versus 21% for cytology and 42% for che st x-ray) but had lower specificity (70 versus 100% for cytology and 9 0% for chest x-ray) than standard methods, Recognizing hnRNP up-regula tion resulted in detection of approximately one-third more early cases than did the combination of X-ray and cytology. Detection of hnRNP A2 /B1 expression appears to be a good initial screening test for lung ca rcinogenesis, as it identified 74% of those who developed subsequent c linical lung cancer, Future studies might separate individuals with hi gh lung cancer risk by MAb detection, confirming the positives with ma rkers having greater specificity (e.g., clinical studies that become p ositive later in the morphological progression).