title: Down-regulation of ECRG4, a candidate tumor suppressor gene, in human breast cancer.
abstract: BACKGROUND
  ECRG4/C2ORF40 is a potential tumor suppressor gene (TSG) recently identified in esophageal carcinoma. Its expression, gene copy number and prognostic value have never been explored in breast cancer.
  
  
  METHODS
  Using DNA microarray and array-based comparative genomic hybridization (aCGH), we examined ECRG4 mRNA expression and copy number alterations in 353 invasive breast cancer samples and normal breast (NB) samples. A meta-analysis was done on a large public retrospective gene expression dataset (n = 1,387) in search of correlations between ECRG4 expression and histo-clinical features including survival.
  
  
  RESULTS
  ECRG4 was underexpressed in 94.3% of cancers when compared to NB. aCGH data revealed ECRG4 loss in 18% of tumors, suggesting that DNA loss is not the main mechanism of underexpression. Meta-analysis showed that ECRG4 expression was significantly higher in tumors displaying earlier stage, smaller size, negative axillary lymph node status, lower grade, and normal-like subtype. Higher expression was also associated with disease-free survival (DFS; HR = 0.84 [0.76-0.92], p = 0.0002) and overall survival (OS; HR = 0.72 [0.63-0.83], p = 5.0E-06). In multivariate analysis including the other histo-clinical prognostic features, ECRG4 expression remained the only prognostic factor for DFS and OS.
  
  
  CONCLUSIONS
  Our data suggest that ECRG4 is a candidate TSG in breast cancer, the expression of which may help improve the prognostication. If functional analyses confirm this TSG role, restoring ECRG4 expression in the tumor may represent a promising therapeutic approach.
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR891 INSERM and Institut Paoli-Calmettes Marseille, Marseille, France.
authors: Renaud
authors: R
authors: Sabatier
authors: Pascal
authors: P
authors: Finetti
authors: José
authors: J
authors: Adelaide
authors: Arnaud
authors: A
authors: Guille
authors: Jean-Paul
authors: JP
authors: Borg
authors: Max
authors: M
authors: Chaffanet
authors: Lydie
authors: L
authors: Lane
authors: Daniel
authors: D
authors: Birnbaum
authors: François
authors: F
authors: Bertucci
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
chemical_list: C476999:ECRG4 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins