Down-Regulation of ECRG4, a Candidate Tumor Suppressor Gene, in Human Breast Cancer
| Autor: | Lydie Lane, José Adélaïde, Max Chaffanet, Pascal Finetti, Renaud Sabatier, Jean-Paul Borg, Daniel Birnbaum, François Bertucci, Arnaud Guille |
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| Přispěvatelé: | Bertucci, François, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM / U891 Inserm), Institut Paoli-Calmettes, Département de science des protéines humaines [Genève], Université de Genève = University of Geneva (UNIGE)-Faculté de médecine [Genève] |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Tumor Physiology
Gene Identification and Analysis Gene Expression lcsh:Medicine Bioinformatics Neoplasm Proteins/genetics Basic Cancer Research Breast Tumors Genes Tumor Suppressor Copy-number variation lcsh:Science ComputingMilieux_MISCELLANEOUS Oligonucleotide Array Sequence Analysis Multidisciplinary Middle Aged Candidate Tumor Suppressor Gene Neoplasm Proteins Oncology Medicine Female DNA microarray Research Article Breast Neoplasms/genetics/pathology Tumor suppressor gene RNA Messenger/genetics/metabolism Down-Regulation Breast Neoplasms [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Molecular Genetics Breast cancer [SDV.CAN] Life Sciences [q-bio]/Cancer medicine Genetics Cancer Genetics Humans Gene Regulation RNA Messenger ddc:576 Gene Expression Profiling Tumor Suppressor Proteins lcsh:R Cancer Computational Biology Cancers and Neoplasms medicine.disease Survival Analysis Gene expression profiling Genetics of Disease Cancer research lcsh:Q Comparative genomic hybridization |
| Zdroj: | PLoS ONE PLoS ONE, 2011, 6 (11), pp.e27656. ⟨10.1371/journal.pone.0027656⟩ PLoS ONE, Vol 6, Iss 11, p e27656 (2011) PLOS ONE, Vol. 6, No 11 (2011) P. e27656 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0027656⟩ |
| Popis: | Introduction 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. |
| Databáze: | OpenAIRE |
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