Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer.

Abstract

Serum biomarkers are not in routine clinical use for diagnosis, prognosis, or treatment selection in lung cancer. We examined serum protein biomarkers from patients with metastatic lung cancer to determine whether they correlate with progression-free survival (PFS), overall survival (OS), or histologic subtype. Serum samples were collected prior to chemotherapy from 153 patients with metastatic lung cancer treated at Memorial Sloan-Kettering Cancer Center. Serum biomarkers were selected for ELISA testing based on their availability in a CLIA-certified clinical laboratory: ProGRP, SCC-Ag, NSE, CYFRA 21-1, TIMP1, and HE4. Pretreatment biomarker levels were correlated with outcome using proportional hazards analysis and tumor histology using logistic regression analysis. Univariate analysis indicated that only higher levels of CYFRA 21-1 were significantly associated with worsened PFS (HR 1.3, 95% CI 1.1--1.5, p< 0.01) and OS (HR 1.4, 95% CI 1.2-1.7, p< 0.001). Multivariate analysis of NSE, CYFRA 21-1, and TIMP1 indicated that CYFRA 21-1 remained independently associated with lower OS (HR 1.3, 95% CI 1.1-1.6, p< 0.01). Univariate analysis indicated that ProGRP (OR 3.3, 95% CI 1.7-6.5, p< 0.001) and NSE (OR 4.8, 95% CI 2.6-8.8, p< 0.0001) had the highest probabilities of differentiating SCLC from NSCLC. Multivariate analysis of these two markers demonstrated that they predicted SCLC histology with 94% accuracy. Univariate analysis showed that only SCCL-Ag distinguished squamous cell histology from adenocarcinoma (OR 4.4, 95% CI 1.7-11.5, p< 0.01). Serum CYFRA 21-1 may be useful in predicting patient survival, and serum ProGRP, NSE 21-1, and SCCL-Ag may be helpful in distinguishing between lung cancer sub-types.