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Down-regulation of ECRG4, a candidate tumor suppressor gene, in human breast cancer Sabatier R; Finetti P; Adelaide J; Guille A; Borg JP; Chaffanet M; Lane L; Birnbaum D; Bertucci FPLoS One 2011[]; 6 (11): e27656INTRODUCTION: 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.|*Down-Regulation[MESH]|*Genes, Tumor Suppressor[MESH]|Breast Neoplasms/*genetics/pathology[MESH]|Female[MESH]|Gene Expression Profiling[MESH]|Humans[MESH]|Middle Aged[MESH]|Neoplasm Proteins/*genetics[MESH]|Oligonucleotide Array Sequence Analysis[MESH]|RNA, Messenger/genetics/metabolism[MESH]|Survival Analysis[MESH]|Tumor Suppressor Proteins[MESH] |