Network-based approach to identify prognostic biomarkers for estrogen receptor-positive breast cancer treatment with tamoxifen
Network-based approach to identify prognostic biomarkers for estrogen receptor-positive breast cancer treatment with tamoxifen
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DOI：
10.1080/15384047.2014.1002360
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发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Zhou, Hong-Hao
中科院分区：
文献类型：
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作者：
Liu, Rong;Guo, Cheng-Xian;Zhou, Hong-Hao
本研究的目的是通过人类mRNA研究来确定与雌激素受体阳性（ER+）乳腺癌相关的有效基因网络和预后生物标志物。利用复杂的ER+乳腺癌转录组进行加权基因共表达网络分析，以研究网络和关键基因在乳腺癌预后中的功能。我们发现表达模块与无远处转移生存率显著相关（发现集HR = 2.25; 95%CI = 21.03 -4.88;验证集HR = 1.78; 95%CI = 1.07-2.93）。该模块包含在M期的生物过程中富集的基因。从这个模块中，我们进一步鉴定和验证了5个枢纽基因（CDK 1，DLGAP 5，MELK，NUSAP 1和RRM 2），其表达水平与生存率低密切相关。高表达MELK表明管腔A和管腔B乳腺癌分子亚型的生存率低。该基因也被发现与他莫昔芬耐药性有关。结果表明，基于网络的方法可能有助于发现ER+乳腺癌预后的生物标志物，也可用作建立个性化治疗的基础。然而，在将该方法应用于临床之前，还需要进行体内外实验和多中心随机对照临床试验。
This study aims to identify effective gene networks and prognostic biomarkers associated with estrogen receptor positive (ER+) breast cancer using human mRNA studies. Weighted gene coexpression network analysis was performed with a complex ER+ breast cancer transcriptome to investigate the function of networks and key genes in the prognosis of breast cancer. We found a significant correlation of an expression module with distant metastasis-free survival (HR = 2.25; 95% CI .21.03-4.88 in discovery set; HR = 1.78; 95% CI = 1.07-2.93 in validation set). This module contained genes enriched in the biological process of the M phase. From this module, we further identified and validated 5 hub genes (CDK1, DLGAP5, MELK, NUSAP1, and RRM2), the expression levels of which were strongly associated with poor survival. Highly expressed MELK indicated poor survival in luminal A and luminal B breast cancer molecular subtypes. This gene was also found to be associated with tamoxifen resistance. Results indicated that a network-based approach may facilitate the discovery of biomarkers for the prognosis of ER+ breast cancer and may also be used as a basis for establishing personalized therapies. Nevertheless, before the application of this approach in clinical settings, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed.