Santpere Gabriel, Alcaráz-Sanabria Ana, Corrales-Sánchez Verónica, Pandiella Atanasio, Győrffy Balázs, Ocaña Alberto
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.
Translational Research Unit and CIBERONC, Albacete University Hospital, Albacete, Spain.
Oncotarget. 2017 Dec 8;9(1):453-463. doi: 10.18632/oncotarget.23065. eCollection 2018 Jan 2.
In breast cancer, it is unclear the functional modifications at a transcriptomic level that are associated with the evolution from epithelial cells and ductal carcinoma (DCIS) to basal-like tumors. By applying weighted gene co-expression network analysis (WGCNA), we identified 17 gene co-expression modules in normal, DCIS and basal-like tumor samples. We then correlated the expression pattern of these gene modules with disease progression from normal to basal-like tumours and found eight modules exhibiting a high and statistically significant correlation. M4 included genes mainly related to cell cycle/division and DNA replication like CCNA2 or CDK1. The M7 module included genes linked with the immune response showing top hub genes such as CD86 or PTPRC. M10 was found specifically correlated to DCIS, but not to basal-like tumor samples, and showed enrichment in ubiquitination or ubiquitin-like processes. We observed that genes in some of these modules were associated with clinical outcome and/or represented druggable opportunities, including AURKA, AURKB, PLK1, MCM2, CDK1, YWHAE, HSP90AB1, LCK, or those targeting ubiquitination. In conclusion, we describe relevant gene modules related to biological functions that can influence survival and be targeted pharmacologically.
在乳腺癌中，尚不清楚从上皮细胞和导管原位癌（DCIS）演变为基底样肿瘤过程中在转录组水平上的功能修饰。通过应用加权基因共表达网络分析（WGCNA），我们在正常、DCIS和基底样肿瘤样本中鉴定出17个基因共表达模块。然后，我们将这些基因模块的表达模式与从正常到基底样肿瘤的疾病进展相关联，发现有八个模块呈现出高度且具有统计学意义的相关性。M4包含主要与细胞周期/分裂和DNA复制相关的基因，如CCNA2或CDK1。M7模块包含与免疫反应相关的基因，显示出诸如CD86或PTPRC等顶级中心基因。发现M10与DCIS特异性相关，但与基底样肿瘤样本无关，并在泛素化或类泛素化过程中表现出富集。我们观察到这些模块中的一些基因与临床结果相关和/或代表了可药物靶向的机会，包括AURKA、AURKB、PLK1、MCM2、CDK1、YWHAE、HSP90AB1、LCK，或那些靶向泛素化的基因。总之，我们描述了与生物学功能相关的重要基因模块，这些模块可影响生存并可作为药物靶点。
