title: A 50-gene signature is a novel scoring system for tumor-infiltrating immune cells with strong correlation with clinical outcome of stage I/II non-small cell lung cancer.
abstract: OBJECTIVE
  To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed.
  
  
  RESULTS
  Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p < 0.0001) and CD20 (p < 0.05) were predictors for RFS, while CD79 and K-RAS mutations showed a tendency.
  
  
  CONCLUSIONS
  Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies.
authors.affiliation: Departamento de AnatomiaPatologica, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos (HCSC), C/Martin Lagos, s/n, Madrid, 28040, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Hernández-Prieto
authors.forename: A
authors.initials: A
authors.lastname: Romera
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
authors.forename: J L
authors.initials: JL
authors.lastname: Subiza
authors.forename: J A
authors.initials: JA
authors.lastname: López-Asenjo
authors.forename: J R
authors.initials: JR
authors.lastname: Jarabo
authors.forename: A M
authors.initials: AM
authors.lastname: Gómez
authors.forename: Elena M
authors.initials: EM
authors.lastname: Molina
authors.forename: J
authors.initials: J
authors.lastname: Puente
authors.forename: J L
authors.initials: JL
authors.lastname: González-Larriba
authors.forename: F
authors.initials: F
authors.lastname: Hernando
authors.forename: B
authors.initials: B
authors.lastname: Pérez-Villamil
authors.forename: E
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: J
authors.initials: J
authors.lastname: Sanz-Ortega
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging
chemical_list: D009363:Neoplasm Proteins