title: Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer.
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.
authors.affiliation: Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Camelia
authors.initials: C
authors.lastname: Sima
authors.affiliation: Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Gonzalez-Espinoza
authors.affiliation: Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Fleisher
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.affiliation: Department of Medicine, Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: CYFRA 21-1; Lung cancer; SCCL-Ag; biomarker panel; biomarkers