A breast cancer classification and immune landscape analysis based on cancer stem-cell-related risk panel.
A breast cancer classification and immune landscape analysis based on cancer stem-cell-related risk panel.
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DOI：
10.1038/s41698-023-00482-w
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发表时间：
2023-12-08
影响因子：
7.9
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究旨在确定乳腺癌（BC）的分子亚型，并开发乳腺癌干细胞（BCSC）相关基因风险评分，用于预测预后和评估免疫治疗的潜力。基于预后BCSC基因的无监督聚类用于确定BC分子亚型。采用加权基因共表达网络分析（WGCNA）筛选非负矩阵分解算法（NMF）确定的BC亚型核心基因。使用机器学习以及LASSO回归和多变量考克斯回归构建基于预后BCSC基因的风险模型。分别使用ESTIMATE和CIBERSORT分析肿瘤微环境和免疫浸润。鉴定CD 79 A + CD 24-PANCK+-BCSC亚群，并通过多重定量免疫荧光（QIF）和TissueFAXS细胞计数法评估其与微环境免疫应答状态的空间关系。我们鉴定了两种不同的分子亚型，其中簇1显示出更好的预后和增强的免疫应答。所构建的涉及10个BCSC基因的风险模型可以有效地将患者分成具有不同生存期、免疫细胞丰度和对免疫治疗的反应的亚组。在随后涉及267名患者的QIF验证中，我们证明了BC组织中存在CD 79 A + CD 24-PANCK+-BCSC，并揭示了该BCSC亚型位于接近耗尽的CD 8 + FOXP 3 + T细胞。此外，CD 79 A + CD 24-PANCK+-BCSC和CD 8 + FOXP 3 +T细胞的密度均与不良存活率呈正相关。这些发现强调了BCSC在预后和重塑免疫微环境中的重要性，这可能为改善患者的预后提供了一种选择。
This study sought to identify molecular subtypes of breast cancer (BC) and develop a breast cancer stem cells (BCSCs)-related gene risk score for predicting prognosis and assessing the potential for immunotherapy. Unsupervised clustering based on prognostic BCSC genes was used to determine BC molecular subtypes. Core genes of BC subtypes identified by non-negative matrix factorization algorithm (NMF) were screened using weighted gene co-expression network analysis (WGCNA). A risk model based on prognostic BCSC genes was constructed using machine learning as well as LASSO regression and multivariate Cox regression. The tumor microenvironment and immune infiltration were analyzed using ESTIMATE and CIBERSORT, respectively. A CD79A+CD24-PANCK+-BCSC subpopulation was identified and its spatial relationship with microenvironmental immune response state was evaluated by multiplexed quantitative immunofluorescence (QIF) and TissueFAXS Cytometry. We identified two distinct molecular subtypes, with Cluster 1 displaying better prognosis and enhanced immune response. The constructed risk model involving ten BCSC genes could effectively stratify patients into subgroups with different survival, immune cell abundance, and response to immunotherapy. In subsequent QIF validation involving 267 patients, we demonstrated the existence of CD79A+CD24-PANCK+-BCSC in BC tissues and revealed that this BCSC subtype located close to exhausted CD8+FOXP3+ T cells. Furthermore, both the densities of CD79A+CD24-PANCK+-BCSCs and CD8+FOXP3+T cells were positively correlated with poor survival. These findings highlight the importance of BCSCs in prognosis and reshaping the immune microenvironment, which may provide an option to improve outcomes for patients.
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颗粒体蛋白前体通过上调肿瘤相关巨噬细胞 (TAM) 上的 PD-L1 表达并促进 CD8( ) T 细胞排斥来诱导乳腺癌免疫逃逸
DOI：
10.1186/s13046-020-01786-6
发表时间：
2021-01-04
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Fang W;Zhou T;Shi H;Yao M;Zhang D;Qian H;Zeng Q;Wang Y;Jin F;Chai C;Chen T
通讯作者：
Chen T
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
生物信息学揭示乳腺癌中巨噬细胞标记基因特征以预测预后
影响因子：
4.4
作者：
Li Y;Zhao X;Liu Q;Liu Y
通讯作者：
Liu Y
DOI：
10.1007/978-3-319-67577-0_4
发表时间：
2017-01-01
期刊：
TUMOR IMMUNE MICROENVIRONMENT IN CANCER PROGRESSION AND CANCER THERAPY
影响因子：
--
作者：
Frankel, Timothy;Lanfranca, Mirna Perusina;Zou, Weiping
通讯作者：
Zou, Weiping
影响因子：
3.1
作者：
Abu El Abbass, Khlood;Abdellateif, Mona S.;Bahnassy, Abeer A.
通讯作者：
Bahnassy, Abeer A.