Abstract
Background:
Serum biomarkers are not in routine clinical use for diagnosis, prognosis, or treatment selection in lung cancer.
Objective:
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.
Methods:
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.
Results:
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).
Conclusions:
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.