Analysis of a panel of serum biomarkers in patients with metastatic lung cancer.

Abstract

e18080 Background: To date, there is no blood test or panel of serum biomarkers commonly used for diagnosis, prognosis or management of patients with lung cancer. We hypothesized that selected protein biomarkers measured in the serum of patients with metastatic lung cancer may correlate with patient survival, or assist in distinguishing between histologic subtypes (squamous vs. adenocarcinoma vs. small cell). Methods: After informed consent, we compiled and analyzed baseline samples of serum prior to chemotherapy from 52 patients with metastatic non-small cell (NSCLC) or small cell lung cancer (SCLC). ELISA was performed on 96-well plates using a robotic plate analyzer in the MSKCC Clinical Laboratory. Selected biomarkers tested to date include: pro-GRP, SCCL, neuron-specific enolase (NSE), CyFra-21. Baseline (pre-treatment) levels have been correlated with patient outcome (proportional hazards method) and tumor histology (logistic regression method) using a prospectively maintained clinical database. Results: Baseline serum levels of CyFra-21 significantly predicted increased risk of mortality (HR 1.4, 95% CI 1.1-1.9, p = 0.01). No association was found between baseline NSE, pro-GRP, and SCCL levels and survival. Preliminary results comparing NSCLC versus SCLC indicate significantly higher levels of NSE (p < 0.03) and pro-GRP (< 0.001), and lower levels of CyFra-21 (p < 0.02), in SCLC. A multivariate logistic model that includes NSE, pro-GRP and CyFra-21 distinguished between SCLC and NSCLC with almost perfect accuracy (C Index = 0.98). Conclusions: Serum biomarkers may be useful in predicting patient survival and distinguishing NSCLC from SCLC. Increased levels of CyFra-21 at the time of diagnosis may be associated with increased mortality. SCLC is associated with higher levels of NSE and pro-GRP, and with lower levels of CyFra-21. There is indication that a valuable prediction instrument can be built using these three markers. Serum analysis is ongoing using samples from 4 timepoints in up to 230 patients. Measurements of the following additional_serum markers are planned: HE-4, mesothelin, osteopontin, CEA, alpha-1 antitrypsin, TTF-1, VEGFR and EGFR. No significant financial relationships to disclose.