Wang Jian, Jiang Haiming
Department of Breast Vascular Intervention, Qingzhou People's Hospital, Qingzhou, Shandong, China.
Department of General Surgery, Qingzhou People's Hospital, Qingzhou, Shandong, China.
Front Genet. 2024 Jul 2;15:1406426. doi: 10.3389/fgene.2024.1406426. eCollection 2024.
To screen mitochondrial function-associated PCD-related biomarkers and construct a risk model for predicting the prognosis of early breast cancer. Data on gene expression levels and clinical information were obtained from the TCGA database, and GSE42568 and GSE58812 datasets were obtained from GEO database. The mitochondrial function-associated programmed cell death (PCD) related genes in early breast cancer were identified, then LASSO logistic regression, SVM-RFE, random forest (RF), and multiple Cox logistic regression analysis were employed to construct a prognostic risk model. Differences in immune infiltration, drug sensitivity, and immunotherapy response were evaluated between groups. Lastly, the qRT-PCR was employed to confirm the key genes. Total 1,478 DEGs were screened between normal and early breast cancer groups, and these DEGs were involved in PI3K-Akt signaling pathway, focal adhesion, and ECM-receptor interaction pathways. Then total 178 mitochondrial function-associated PCD related genes were obtained, followed by a four mitochondrial function-associated PCD related genes prognostic model and nomogram were built. In addition, total 2 immune checkpoint genes were lowly expressed in the high-risk group, including CD47 and LAG3, and the fraction of some immune cells in high- and low-risk groups had significant difference, such as macrophage, eosinophil, mast cell, etc., and the Top3 chemotherapeutics with significant differences were included FH535, MK.2206, and bicalutamide. Finally, the qRT-qPCR results shown that the CREB3L1, CAPG, SPINT1 and GRK3 mRNA expression were in line with the bioinformatics analysis results. Four mitochondrial function-associated PCD-related genes were identified, including CREB3L1, CAPG, SPINT1, and GRK3, and the prognostic risk model and nomogram were established for predicting the survival of early breast cancer patient. The chemotherapeutics, containing FH535, MK.2206, and bicalutamide, might be used for early breast cancer.
筛选与线粒体功能相关的程序性细胞死亡（PCD）相关生物标志物，并构建预测早期乳腺癌预后的风险模型。从TCGA数据库获取基因表达水平数据和临床信息，从GEO数据库获取GSE42568和GSE58812数据集。鉴定早期乳腺癌中线粒体功能相关的程序性细胞死亡（PCD）相关基因，然后采用LASSO逻辑回归、支持向量机递归特征消除（SVM-RFE）、随机森林（RF）和多元Cox逻辑回归分析构建预后风险模型。评估组间免疫浸润、药物敏感性和免疫治疗反应的差异。最后，采用qRT-PCR验证关键基因。正常组和早期乳腺癌组之间共筛选出1478个差异表达基因（DEG），这些DEG参与PI3K-Akt信号通路、粘着斑和细胞外基质-受体相互作用通路。然后获得了总共178个与线粒体功能相关的PCD相关基因，接着构建了一个由四个与线粒体功能相关的PCD相关基因组成的预后模型和列线图。此外，高危组中共有2个免疫检查点基因低表达，包括CD47和LAG3，高危组和低危组中一些免疫细胞的比例有显著差异，如巨噬细胞、嗜酸性粒细胞、肥大细胞等，差异显著的前3种化疗药物包括FH535、MK.2206和比卡鲁胺。最后，qRT-qPCR结果显示，CREB3L1、CAPG、SPINT1和GRK3 mRNA表达与生物信息学分析结果一致。鉴定出四个与线粒体功能相关的PCD相关基因，包括CREB3L1、CAPG、SPINT1和GRK3，并建立了预测早期乳腺癌患者生存的预后风险模型和列线图。含有FH535、MK.2206和比卡鲁胺的化疗药物可能用于早期乳腺癌。
