Integrated analysis reveals the molecular features of fibrosis in triple-negative breast cancer

被引：34

作者：

Ding, Jia-Han ^{[1
]}

Xiao, Yi ^{[1
]}

Zhao, Shen ^{[1
]}

Xu, Ying ^{[1
]}

Xiao, Yu-Ling ^{[1
]}

Shao, Zhi-Ming ^{[1
,2
]}

Jiang, Yi-Zhou ^{[1
]}

Di, Gen-Hong ^{[1
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Shanghai Med Coll, Dept Breast Surg,Dept Oncol,Key Lab Breast Canc S, Shanghai 200032, Peoples R China

[2] Fudan Univ, Precis Canc Med Ctr, Shanghai Canc Ctr, Shanghai 200032, Peoples R China

来源：

MOLECULAR THERAPY ONCOLYTICS | 2022年 / 24卷

基金：

中国国家自然科学基金;

关键词：

FIBROTIC FOCUS; TGF-BETA; EXPRESSION; CARCINOMAS; HYPOXIA; MARKER; RAC1;

D O I：

10.1016/j.omto.2022.02.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：624 / 635

页数：12

共 62 条

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