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

Article type: Research Article

Authors: Lou, Emil^a | Johnson, Melissa^b | Sima, Camelia^c | Gonzalez-Espinoza, Rita^d | Fleisher, Martin^d | Kris, Mark G.^e | Azzoli, Christopher G.^{f; *}

Affiliations: [a] Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA | [b] Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA | [c] Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA | [d] Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA | [e] Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA | [f] Department of Medicine, Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA

Correspondence: [*] Corresponding author: Christopher G. Azzoli, Hematology/Oncology, 55 Fruit Street, Boston, MA 02114-2696, USA. E-mail: cazzoli@partners.org.

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.

Keywords: Lung cancer, biomarkers, biomarker panel, CYFRA 21-1, SCCL-Ag

DOI: 10.3233/CBM-140399

Journal: Cancer Biomarkers, vol. 14, no. 4, pp. 207-214, 2014