Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated with Estrogen Receptor-Negative Subtypes and Poor Prognosis.
Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated with Estrogen Receptor-Negative Subtypes and Poor Prognosis.
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DOI：
10.1016/j.ebiom.2015.01.008
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发表时间：
2015-03
期刊：
影响因子：
11.1
通讯作者：
Levine, Beth
中科院分区：
文献类型：
--
作者：
Tang, Hao;Sebti, Salwa;Titone, Rossella;Zhou, Yunyun;Isidoro, Ciro;Ross, Theodora S.;Hibshoosh, Hanina;Xiao, Guanghua;Packer, Milton;Xie, Yang;Levine, Beth
BRCA1和Beclin 1(BECN1)均为肿瘤抑制基因，位于人类染色体17q21乳腺癌易感基因座附近，常同时缺失。然而，它们在散发性人类乳腺癌中的重要性尚不清楚。为了探讨BECN1和BRCA1在乳腺癌中的作用，我们从两个大型数据库中研究了BECN1和BRCA1在乳腺癌患者中的表达模式：癌症基因组图谱(TCGA)(n=1067)和乳腺癌国际联合会分子分类(METABRIC)(n=91992)。在这两个数据集中，与腔内A/B固有肿瘤亚型相比，BECN1低表达在HER2富集型和基底样型(大多为三阴性)乳腺癌中更为常见，并且与TP53突变和晚期肿瘤分级密切相关。相反，BRCA1的低表达与HER2富集型或碱基样亚型、TP53突变或肿瘤分级之间没有显著的关联。此外，BECN1的低表达(而不是BRCA1的低表达)与预后不良有关，而BECN1(而不是BRCA1)的表达是预后的独立预测因素。这些发现表明，自噬基因BECN1的mRNA表达降低可能与HER2富集型、基底样癌和TP53突变乳腺癌的发生和发展有关。肿瘤抑制基因BECN1和BRCA1与17q21乳腺癌易感基因密切相关。我们在大型TCGA和METABRIC数据集中研究了乳腺癌患者中BECN1和BRCA1的mRNA表达模式。BECN1(而不是BRCA1)的表达降低与乳腺癌的侵袭性临床病理特征有关。在人类乳腺癌患者中，BECN1(但不是BRCA1)表达降低与生存率下降有关。
Both BRCA1 and Beclin 1 (BECN1) are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA) (n = 1067) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1992). In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly triple-negative) breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers. The tumor suppressor genes, BECN1 and BRCA1, are in close proximity to the 17q21 breast cancer tumor susceptibility locus. We studied mRNA expression patterns of BECN1 and BRCA1 in breast cancer patients in the large TCGA and METABRIC datasets. Decreased BECN1 (but not BRCA1) expression is linked with aggressive clinico-pathological features in human breast cancer. Decreased BECN1 (but not BRCA1) expression is linked with worse survival in human breast cancer patients.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
4.8
作者：
Han, Jie;Hou, Wen;Rabinowich, Hannah
通讯作者：
Rabinowich, Hannah
影响因子：
56.9
作者：
FUTREAL, PA;LIU, QY;WISEMAN, R
通讯作者：
WISEMAN, R
影响因子：
20.3
作者：
Cheng, Chieh-Lung;Hou, Hsin-An;Tien, Hwei-Fang
通讯作者：
Tien, Hwei-Fang
影响因子：
11.1
作者：
Garcia, Amandine I.;Buisson, Monique;Bertrand, Pascale;Rimokh, Ruth;Rouleau, Etienne;Lopez, Bernard S.;Lidereau, Rosette;Mikaelian, Ivan;Mazoyer, Sylvie
通讯作者：
Mazoyer, Sylvie