基于血管生成拟态相关基因的乳腺癌新亚型鉴定及乳腺癌预后预测新模型
Identification of new subtypes of breast cancer based on vasculogenic mimicry related genes and a new model for predicting the prognosis of breast cancer.
作者信息
Liang Xiao, Ma Xinyue, Luan Feiyang, Gong Jin, Zhao Shidi, Pan Yiwen, Liu Yijia, Liu Lijuan, Huang Jing, An Yiyang, Hu Sirui, Yang Jin, Dong Danfeng
机构信息
Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
出版信息
Heliyon. 2024 Aug 20;10(17):e36565. doi: 10.1016/j.heliyon.2024.e36565. eCollection 2024 Sep 15.
Breast cancer is a malignant tumor that poses a serious threat to women's health, and vasculogenic mimicry (VM) is strongly associated with bad prognosis in breast cancer. However, the relationship between VM and immune infiltration in breast cancer and the underlying mechanisms have not been fully studied. On the basis of the Cancer Genome Atlas (TCGA), Fudan University Shanghai Cancer Center (FUSCC) database, GSCALite database, and gene set enrichment analysis (GSEA) datasets, we investigated the potential involvement of VM-related genes in the development and progression of breast cancer. We analyzed the differential expression, mutation status, methylation status, drug sensitivity, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoints, tumor microenvironment (TME), and immune cell infiltration levels associated with VM-related genes in breast cancer. We created two VM subclusters out of breast cancer patients using consensus clustering, and discovered that patients in Cluster 1 had better survival outcomes compared to those in Cluster 2. The infiltration levels of T cells CD4 memory resting and T cells CD8 were higher in Cluster 1, indicating an immune-active state in this cluster. Additionally, we selected three prognostic genes (LAMC2, PIK3CA, and TFPI2) using Lasso, univariate, and multivariate Cox regression and constructed a risk model, which was validated in an external dataset. The prognosis of patients is strongly correlated with aberrant expression of VM-related genes, which advances our knowledge of the tumor immune milieu and enables us to identify previously unidentified breast cancer subtypes. This could direct more potent immunotherapy approaches.
乳腺癌是一种对女性健康构成严重威胁的恶性肿瘤,而血管生成拟态(VM)与乳腺癌的不良预后密切相关。然而,VM与乳腺癌免疫浸润之间的关系及其潜在机制尚未得到充分研究。基于癌症基因组图谱(TCGA)、复旦大学附属肿瘤医院(FUSCC)数据库、GSCALite数据库和基因集富集分析(GSEA)数据集,我们研究了VM相关基因在乳腺癌发生发展中的潜在作用。我们分析了与乳腺癌中VM相关基因有关的差异表达、突变状态、甲基化状态、药物敏感性、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、免疫检查点、肿瘤微环境(TME)和免疫细胞浸润水平。我们使用一致性聚类从乳腺癌患者中创建了两个VM亚组,发现与第2组患者相比,第1组患者的生存结果更好。第1组中T细胞CD4记忆静止细胞和T细胞CD8的浸润水平较高,表明该组处于免疫激活状态。此外,我们使用套索回归、单变量和多变量Cox回归选择了三个预后基因(LAMC2、PIK3CA和TFPI2)并构建了一个风险模型,该模型在外部数据集中得到了验证。患者的预后与VM相关基因的异常表达密切相关,这加深了我们对肿瘤免疫环境的认识,并使我们能够识别以前未被识别的乳腺癌亚型。这可以指导更有效的免疫治疗方法。