Integrated analysis reveals the molecular features of fibrosis in triple-negative breast cancer.
Integrated analysis reveals the molecular features of fibrosis in triple-negative breast cancer.
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综合分析揭示了三阴性乳腺癌纤维化的分子特征
DOI：
10.1016/j.omto.2022.02.003
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发表时间：
2022-03-17
期刊：
影响因子：
--
通讯作者：
Di GH
中科院分区：
文献类型：
--
作者：
Ding JH;Xiao Y;Zhao S;Xu Y;Xiao YL;Shao ZM;Jiang YZ;Di GH
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌。以胶原纤维增加为标志的高度纤维化在TNBC中广泛存在，并与肿瘤进展相关。然而，纤维化的分子特征及其导致预后不良的原因仍然知之甚少。基于TNBC的多组学数据集，我们评估了344个样本的病理纤维化分级以供进一步分析。分析了不同纤维化亚组的基因组、转录组和免疫变化。高纤维化是一个独立的不良预后预测因子，并与低基质肿瘤浸润淋巴细胞的相互作用。基因组分析将6p22.2-6p22.1（TRIM 27）和20q13.33（CDH 4）的拷贝数增加确定为具有高度纤维化的肿瘤的基因组标志。转录组分析显示，转化生长因子-β通路和缺氧通路是高纤维化肿瘤的关键促癌通路。此外，我们系统地评估了纤维化与不同类型的免疫和基质细胞之间的关系。具有高度纤维化的肿瘤的特征在于免疫抑制性肿瘤微环境，具有有限的免疫细胞浸润和增加的成纤维细胞。这项研究提出了新的见解基因组和转录组学的改变可能驱动纤维化。此外，纤维化与免疫抑制肿瘤微环境有关，导致预后不良。纤维化表明三阴性乳腺癌（TNBC）的预后不良。对于大型多组学TNBC队列，Di et al.系统地揭示了纤维化TNBC的基因组改变和免疫抑制微环境。转化生长因子（TGF）-β通路可能减少免疫细胞浸润，诱导免疫抑制环境，导致TNBC患者预后不良。
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer. High fibrosis, marked by increased collagen fibers, is widespread in TNBC and correlated with tumor progression. However, the molecular features of fibrosis and why it results in a poor prognosis remain poorly understood. Based on multiomics datasets of TNBC, we evaluated the pathological fibrosis grade of 344 samples for further analysis. Genomic, transcriptomic, and immune changes were analyzed among different subgroups of fibrosis. High fibrosis was an independent adverse prognosis predictor and had interactions with low stromal tumor-infiltrating lymphocytes. Genomic analysis identified copy number gains of 6p22.2–6p22.1 (TRIM27) and 20q13.33 (CDH4) as genomic hallmarks of tumors with high fibrosis. Transcriptome analysis revealed the transforming growth factor-beta pathway and hypoxia pathway were key pro-oncogenic pathways in tumors with high fibrosis. Moreover, we systematically evaluate the relationship between fibrosis and different kinds of immune and stromal cells. Tumors with high fibrosis were characterized by an immunosuppressive tumor microenvironment with limited immune cell infiltration and increased fibroblasts. This study proposes new insight into the genomic and transcriptomic alterations potentially driving fibrosis. Moreover, fibrosis is related to an immunosuppressive tumor microenvironment that contributes to the poor prognosis. Fibrosis indicates a poor prognosis in triple-negative breast cancer (TNBC). With a large multi-omic TNBC cohort, Di et al. systematically revealed the genomic alterations and immunosuppressive microenvironment of fibrotic TNBCs. transforming growth factor (TGF)-β pathway might decrease immune cell infiltration and induce the immunosuppressive environment, which resulted in a poor prognosis for patients with TNBC.
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影响因子：
1.9
作者：
Aziz, Ahmad Aizat Abdul;Salleh, Md Salzihan Md;Ankathil, Ravindran
通讯作者：
Ankathil, Ravindran
DOI：
10.18632/aging.104163
发表时间：
2020-12-02
期刊：
Aging
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.6
作者：
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影响因子：
39.3
作者：
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通讯作者：
Ten Dijke P
三阴性乳腺癌的基因组和转录组景观：亚型和治疗策略
影响因子：
50.3
作者：
Jiang, Yi-Zhou;Ma, Ding;Shao, Zhi-Ming
通讯作者：
Shao, Zhi-Ming