Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR891 INSERM and Institut Paoli-Calmettes Marseille, Marseille, France.
PLoS One. 2011;6(11):e27656. doi: 10.1371/journal.pone.0027656. Epub 2011 Nov 16.
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.
ECRG4/C2ORF40 是最近在食管癌中发现的一种潜在的肿瘤抑制基因（TSG）。其在乳腺癌中的表达、基因拷贝数和预后价值尚未得到探索。
我们使用 DNA 微阵列和基于阵列的比较基因组杂交（aCGH）技术，检测了 353 例浸润性乳腺癌样本和正常乳腺（NB）样本中 ECRG4 mRNA 的表达和拷贝数改变。我们对一个大型公共回顾性基因表达数据集（n=1387）进行了荟萃分析，以寻找 ECRG4 表达与包括生存在内的组织学和临床特征之间的相关性。
与 NB 相比，ECRG4 在 94.3%的癌症中表达下调。aCGH 数据显示，18%的肿瘤存在 ECRG4 缺失，提示 DNA 缺失不是表达下调的主要机制。荟萃分析显示，ECRG4 在更早的分期、更小的肿瘤大小、阴性腋窝淋巴结状态、更低的分级和正常样亚型的肿瘤中表达更高。较高的表达与无病生存（DFS；HR=0.84 [0.76-0.92]，p=0.0002）和总生存（OS；HR=0.72 [0.63-0.83]，p=5.0E-06）相关。在包括其他组织学和临床预后特征的多变量分析中，ECRG4 表达仍然是 DFS 和 OS 的唯一预后因素。
我们的数据表明，ECRG4 是乳腺癌的候选 TSG，其表达可能有助于改善预后。如果功能分析证实了这种 TSG 作用，那么在肿瘤中恢复 ECRG4 的表达可能代表了一种有前途的治疗方法。
