Yu Daowu, Liu Shengwei, Chen Yijun, Yang Lumeng
Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Front Genet. 2022 Jul 12;13:944259. doi: 10.3389/fgene.2022.944259. eCollection 2022.
In light of the limited number of targetable oncogenic drivers in breast cancer (BRCA), it is important to identify effective and druggable gene targets for the treatment of this devastating disease. Herein, the GSE102484 dataset containing expression profiling data from 683 BRCA patients was re-analyzed using weighted gene co-expression network analysis (WGCNA). The yellow module with the highest correlation to BRCA progression was screened out, followed by functional enrichment analysis and establishment of a protein-protein interaction (PPI) network. After further validation through survival analysis and expression evaluation, CHEK1 and UBE2C were finally identified as hub genes related to the progression of BRCA, especially the luminal A breast cancer subtype. Notably, both hub genes were found to be dysregulated in multiple types of immune cells and closely correlated with tumor infiltration, as revealed by Tumor Immune Estimation Resource (TIMER) along with other bioinformatic tools. Construction of transcription factors (TF)-hub gene network further confirmed the existence of 11 TFs which could regulate both hub genes simultaneously. Our present study may facilitate the invention of targeted therapeutic drugs and provide novel insights into the understanding of the mechanism beneath the progression of BRCA.
鉴于乳腺癌（BRCA）中可靶向的致癌驱动因子数量有限，确定有效且可成药的基因靶点对于治疗这种毁灭性疾病至关重要。在此，我们使用加权基因共表达网络分析（WGCNA）对包含683例BRCA患者表达谱数据的GSE102484数据集进行了重新分析。筛选出与BRCA进展相关性最高的黄色模块，随后进行功能富集分析并建立蛋白质-蛋白质相互作用（PPI）网络。通过生存分析和表达评估进一步验证后，最终确定CHEK1和UBE2C为与BRCA进展相关的枢纽基因，尤其是管腔A型乳腺癌亚型。值得注意的是，肿瘤免疫估计资源（TIMER）以及其他生物信息学工具显示，这两个枢纽基因在多种免疫细胞中均存在失调，且与肿瘤浸润密切相关。转录因子（TF）-枢纽基因网络的构建进一步证实存在11种可同时调节这两个枢纽基因的转录因子。我们目前的研究可能有助于靶向治疗药物的研发，并为理解BRCA进展背后的机制提供新的见解。
