Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Clin Exp Med. 2023 Nov;23(7):3867-3881. doi: 10.1007/s10238-023-01090-5. Epub 2023 May 23.
Triple negative breast cancer (TNBC) is the most aggressive and malignant subtype in breast cancer. Immunotherapy is a currently promising and effective treatment for TNBC, while not all patients are responsive. Therefore, it is necessary to explore novel biomarkers to screen sensitive populations for immunotherapy. All mRNA expression profiles of TNBC from The Cancer Genome Atlas (TCGA) database were clustered into two subgroups by analyzing tumor immune microenvironment (TIME) with single sample gene set enrichment analysis (ssGSEA). A risk score model was constructed based on differently expressed genes (DEGs) identified from two subgroups using Cox and Least Absolute Shrinkage and Selector Operation (LASSO) regression model. And it was validated by Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) analysis in Gene Expression Omnibus (GEO) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Multiplex immunofluorescence (mIF) and Immunohistochemical (IHC) staining were performed on clinical TNBC tissue samples. The relationship between risk score and immune checkpoint blockades (ICB) related signatures was further investigated, as well as the biological processes were performed by gene set enrichment analysis (GSEA). We obtained three DEGs positively related to prognosis and infiltrating immune cells in TNBC. Our risk score model could be an independent prognostic factor and the low risk group exhibited a prolonged overall survival (OS). Patients in low risk group were more likely to present a higher immune infiltration and stronger response to immunotherapy. GSEA revealed the model was associated with immune-related pathways. We constructed and validated a novel model based on three prognostic genes related to TIME in TNBC. The model contributed a robust signature that could predict the prognosis in TNBC, especially for the efficacy of immunotherapy.
三阴性乳腺癌(TNBC)是乳腺癌中最具侵袭性和恶性的亚型。免疫疗法是目前治疗 TNBC 有前途且有效的方法,但并非所有患者都有反应。因此,有必要探索新的生物标志物,以筛选对免疫治疗敏感的人群。通过对肿瘤免疫微环境(TIME)进行单样本基因集富集分析(ssGSEA),对来自癌症基因组图谱(TCGA)数据库的所有 TNBC mRNA 表达谱进行聚类,分为两个亚组。基于两个亚组中差异表达基因(DEGs),使用 Cox 和最小绝对收缩和选择操作(LASSO)回归模型构建风险评分模型。并通过 Kaplan-Meier 分析和Receiver Operating Characteristic(ROC)分析在基因表达综合数据库(GEO)和乳腺癌国际联合会(METABRIC)数据库中进行验证。对临床 TNBC 组织样本进行多重免疫荧光(mIF)和免疫组织化学(IHC)染色。进一步研究风险评分与免疫检查点阻断(ICB)相关特征之间的关系,并通过基因集富集分析(GSEA)进行生物学过程分析。我们获得了三个与 TNBC 预后和浸润免疫细胞呈正相关的 DEG。我们的风险评分模型可以作为一个独立的预后因素,低风险组表现出更长的总生存期(OS)。低风险组患者更有可能表现出更高的免疫浸润和对免疫治疗的更强反应。GSEA 表明该模型与免疫相关途径有关。我们构建并验证了一个基于 TNBC 中与 TIME 相关的三个预后基因的新型模型。该模型提供了一个稳健的特征,可以预测 TNBC 的预后,特别是对免疫治疗的疗效。