Journal Article

Down-Regulation of ECRG4, a Candidate Tumor Suppressor Gene, in Human Breast Cancer

Finetti, Pascal, Chaffanet, Max, Bertucci, François, Guille, Arnaud, Birnbaum, Daniel, Borg, Jean-Paul, Sabatier, Renaud, Adelaide, José, Lane, Lydie

2011

Overview

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. 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cancer / Cancer genetics / Cancer therapies / Chemotherapy / Clinical trials / Comparative analysis / Copy number / Cytogenetics / Datasets / Deoxyribonucleic acid / DNA / DNA microarrays / Down-Regulation / Epigenetics / Esophageal cancer / Esophageal carcinoma / Esophagus / Female / Gene expression / Gene Expression Profiling / Genes / Genes, Tumor Suppressor / Genetic aspects / Genomics / Humans / Hybridization / Invasiveness / Kinases / Life Sciences / Lymph nodes / Medical prognosis / Medicine / Messenger RNA / Metastasis / Middle Aged / Multivariate analysis / Mutation / Neoplasm Proteins - genetics / Oligonucleotide Array Sequence Analysis / Prognosis / Prostate / RNA, Messenger - genetics / RNA, Messenger - metabolism / Survival / Survival Analysis / Tumor suppressor genes / Tumors