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运用加权基因共表达网络分析(WGCNA)和Cox回归分析鉴定与乳腺癌预后相关的关键转录因子和免疫浸润模式

Identification of Key Transcription Factors and Immune Infiltration Patterns Associated With Breast Cancer Prognosis Using WGCNA and Cox Regression Analysis.

作者信息

Yin Xin, Liu Jiaxiang, Wang Xin, Yang Tianshu, Li Gen, Shang Yaxin, Teng Xu, Yu Hefen, Wang Shuang, Huang Wei

机构信息

Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Front Oncol. 2021 Dec 21;11:742792. doi: 10.3389/fonc.2021.742792. eCollection 2021.

Abstract

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among women worldwide. Therefore, the need for effective breast cancer treatment is urgent. Transcription factors (TFs) directly participate in gene transcription, and their dysregulation plays a key role in breast cancer. Our study identified 459 differentially expressed TFs between tumor and normal samples from The Cancer Genome Atlas database. Based on gene expression analysis and weighted gene co-expression network analysis, the co-expression yellow module was found to be integral for breast cancer progression. A total of 121 genes in the yellow module were used for function enrichment. To further confirm prognosis-related TFs, COX regression and LASSO analyses were performed; consequently, a prognostic risk model was constructed, and its validity was verified. Ten prognosis-related TFs were identified according to their expression profile, survival probability, and target genes. COPS5, HDAC2, and NONO were recognized as hub TFs in breast cancer. These TFs were highly expressed in human breast cancer cell lines and clinical breast cancer samples; this result was consistent with the information from multiple databases. Immune infiltration analysis revealed that the proportions of resting dendritic and mast cells were greater in the low-risk group than those in the high-risk group. Thus, in this study, we identified three hub biomarkers related to breast cancer prognosis. The results provide a framework for the co-expression of TF modules and immune infiltration in breast cancer.

摘要

乳腺癌是全球女性中最常被诊断出的癌症,也是癌症死亡的第二大主要原因。因此,迫切需要有效的乳腺癌治疗方法。转录因子(TFs)直接参与基因转录,其失调在乳腺癌中起关键作用。我们的研究从癌症基因组图谱数据库中鉴定出肿瘤样本和正常样本之间有459个差异表达的转录因子。基于基因表达分析和加权基因共表达网络分析,发现共表达黄色模块对乳腺癌进展至关重要。黄色模块中的总共121个基因用于功能富集。为了进一步确认与预后相关的转录因子,进行了COX回归和LASSO分析;因此,构建了一个预后风险模型,并验证了其有效性。根据其表达谱、生存概率和靶基因鉴定出10个与预后相关的转录因子。COPS5、HDAC2和NONO被认为是乳腺癌中的核心转录因子。这些转录因子在人乳腺癌细胞系和临床乳腺癌样本中高表达;这一结果与多个数据库的信息一致。免疫浸润分析显示,低风险组中静息树突状细胞和肥大细胞的比例高于高风险组。因此,在本研究中,我们鉴定出了三个与乳腺癌预后相关的核心生物标志物。研究结果为乳腺癌中转录因子模块的共表达和免疫浸润提供了一个框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b275/8724129/ba74df8d006b/fonc-11-742792-g001.jpg

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