Validation of a Blood-Based Protein Biomarker Panel for a Risk Assessment of Lethal Lung Cancer in the Physicians’ Health Study

Abstract

This study aimed to assess a four-marker protein panel (4MP)’s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians’ Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61–0.92) and 0.69 (95% CI: 0.56–0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. When stratifying into ever-smokers and never-smokers, the 4MP had respective AUCs of 0.77 (95% CI: 0.63–0.92) and 0.72 (95% CI: 0.17–1.00) for a 1-year risk of lung cancer. The AUCs of the 4MP for predicting metastatic lung cancer within one year and two years of the blood draw were 0.95 (95% CI: 0.87–1.00) and 0.78 (95% CI: 0.62–0.94), respectively. Our findings indicate that a blood-based biomarker panel may be useful in identifying ever- and never-smokers at high risk of a diagnosis of lung cancer within one-to-two years.