title: Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis.
abstract: BACKGROUND
  Immunoregulatory cytokines may play a fundamental role in tumor growth and metastases. Their effects are mediated through complex regulatory networks. Human cytokine profiles could define patient subgroups and represent new potential biomarkers. The aim of this study was to associate a cytokine profile obtained through data mining with the clinical characteristics of patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  We conducted a prospective study of the plasma levels of 14 immunoregulatory cytokines by ELISA and a cytometric bead array assay in 110 NSCLC patients before chemotherapy and 25 control subjects. Cytokine levels and data-mining profiles were associated with clinical, quality of life and pathological outcomes.
  
  
  RESULTS
  NSCLC patients had higher levels of interleukin (IL)-6, IL-8, IL-12p70, IL-17a and interferon (IFN)-γ, and lower levels of IL-33 and IL-29 compared with controls. The pro-inflammatory cytokines IL-1b, IL-6 and IL-8 were associated with lower hemoglobin levels, worse functional performance status (Eastern Cooperative Oncology Group, ECOG), fatigue and hyporexia. The anti-inflammatory cytokines IL-4, IL-10 and IL-33 were associated with anorexia and lower body mass index. We identified three clusters of patients according to data-mining analysis with different overall survival (OS; 25.4, 16.8 and 5.09 months, respectively, P = 0.0012). Multivariate analysis showed that ECOG performance status and data-mining clusters were significantly associated with OS (RR 3.59, [95% CI 1.9-6.7], P < 0.001 and 2.2, [1.2-3.8], P = 0.005).
  
  
  CONCLUSIONS
  Our results provide evidence that complex cytokine networks may be used to identify patient subgroups with different prognoses in advanced NSCLC. These cytokines may represent potential biomarkers, particularly in the immunotherapy era in cancer research.
authors.affiliation: Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City Postgraduate Unit, Faculty of Medicine, National Autonomous University of Mexico, Mexico City.
authors.forename: L
authors.initials: L
authors.lastname: Barrera
authors.affiliation: Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City.
authors.forename: E
authors.initials: E
authors.lastname: Montes-Servín
authors.affiliation: Computer Engineering Department, Mexico's Autonomous Technological Institute, Mexico City.
authors.forename: A
authors.initials: A
authors.lastname: Barrera
authors.affiliation: Laboratory of Experimental Oncology and Thoracic Oncology Unit, National Institute of Cancer, Mexico City.
authors.forename: L A
authors.initials: LA
authors.lastname: Ramírez-Tirado
authors.affiliation: Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City.
authors.forename: F
authors.initials: F
authors.lastname: Salinas-Parra
authors.affiliation: Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City Laboratory of Immunology, National Institute of Cardiology, Ignacio Chávez, Mexico City.
authors.forename: J L
authors.initials: JL
authors.lastname: Bañales-Méndez
authors.affiliation: Division of Natural Sciences, Regional Center for Teacher Development and Educational Research (CRFDIES) of Sonora, Sonora, México.
authors.forename: M
authors.initials: M
authors.lastname: Sandoval-Ríos
authors.affiliation: Postgraduate Unit, Faculty of Medicine, National Autonomous University of Mexico, Mexico City Laboratory of Experimental Oncology and Thoracic Oncology Unit, National Institute of Cancer, Mexico City ogar@unam.mx.
authors.forename: Ó
authors.initials: Ó
authors.lastname: Arrieta
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood*; D057225:Data Mining / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000145:classification / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines
keywords: biomarkers; cytokines; data-mining analysis; non-small-cell lung cancer; prognosis