title: RANTES expression is a predictor of survival in stage I lung adenocarcinoma.
abstract: OBJECTIVE
  The presence of an active lymphocytic response (ALR) in non-small cell lung cancer (NSCLC) tumors has previously been associated with a more favorable prognosis. The purpose of this study was to identify differences in global gene expression profiles between stage I NSCLC tumors with ALR (ALR+) and those without ALR (ALR-).
  
  
  METHODS
  Sixty-three stage I lung adenocarcinomas were analyzed for gene expression using Affymetrix oligonucleotide microarrays. Tumors were stratified into ALR+ and ALR- groups and compared for statistically significant differences in gene expression. Identified candidate genes were validated using both ELISA and immunohistochemistry. Follow-up data for these patients were collected and used to assess patient prognosis.
  
  
  RESULTS
  Of the 63 tumors studied, 27 were ALR+ and 36 were ALR-. A total of 303 genes showed significant differences in gene expression between the two populations (t test, P < 0.02). Three of the genes overexpressed by ALR+ tumors were the chemokines: small inducible cytokine A4 (MIP-1beta), RANTES, and interferon inducible protein 10 (IP-10). Immunohistochemistry analysis showed that the tumor cells expressed these cytokines. ELISA showed that MIP-1beta and RANTES were overexpressed at the protein level by ALR+ tumors. Univariate Cox proportional hazards analysis showed that RANTES was a predictor of survival in stage I lung adenocarcinomas (P = 0.002).
  
  
  CONCLUSIONS
  When tested in the Cox univariate proportional hazards model, RANTES expression by lung adenocarcinoma cells is a predictor of survival in stage I NSCLC patients and may be useful as a prognostic factor in lung cancer.
authors.affiliation: Section of General Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moran
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Arenberg
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
authors.forename: Mark D
authors.initials: MD
authors.lastname: Iannettoni
authors.forename: Mark B
authors.initials: MB
authors.lastname: Orringer
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics* / Q000378:metabolism; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma