Risk Signature of Cancer-Associated Fibroblast-Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer.
Risk Signature of Cancer-Associated Fibroblast-Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer.
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癌症相关成纤维细胞分泌的细胞因子的风险特征与乳腺癌的临床结果相关
DOI：
10.3389/fonc.2021.628677
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发表时间：
2021
影响因子：
4.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Sun C;Wang S;Zhang Y;Yang F;Zeng T;Meng F;Yang M;Yang Y;Hua Y;Fu Z;Li J;Huang X;Wu H;Yin Y;Li W
癌症相关成纤维细胞（CAF）是肿瘤微环境（TME）的关键组成部分。CAFs的分泌产物在调节肿瘤细胞和影响临床预后方面发挥重要作用。本研究旨在通过构建乳腺癌风险特征来揭示CAF分泌的细胞因子与乳腺癌的关系。我们进行了三种算法来揭示TCGA BC数据集中的CAF相关细胞因子，并鉴定了五种与肿瘤相关的细胞因子。然后我们使用BC的单细胞RNA测序（ScRNA-Seq）数据集来确认这五种细胞因子在CAFs中的表达水平。METABRIC和其他独立数据集用于验证进一步分析的结果。基于从CAF中鉴定的五种细胞因子特征，具有高风险评分（RS）的BC患者的总生存期比低RS病例短。进一步分析表明，高RS水平与细胞增殖和肥大细胞浸润的基底样亚型的BCs。结果还表明，RS水平可以区分携带驱动突变的高风险BC病例（即，PI 3 KCA、CDH 1和TP 53）。此外，五细胞因子签名的状态与全基因组复制（WGD）事件的频率和分子时序相关。BC样本的瘤内异质性（ITH）分析表明，高RS水平与肿瘤亚克隆的增加有关。这项工作表明，基于CAF分泌的细胞因子的预后特征与临床结果、肿瘤进展和遗传改变相关。我们的研究结果可能会提供见解，制定新的战略，早期干预和预后预测的BC。
Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.
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影响因子：
16.6
作者：
Cortes-Ciriano I;Lee S;Park WY;Kim TM;Park PJ
通讯作者：
Park PJ
影响因子：
6.6
作者：
Beckham, Carla J.;Olsen, Jayme;Lee, Yi-Fen
通讯作者：
Lee, Yi-Fen
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.
影响因子：
28.2
作者：
Elyada, Ela;Bolisetty, Mohan;Tuveson, David A.
通讯作者：
Tuveson, David A.
影响因子：
50.3
作者：
Costa, Ana;Kieffer, Yann;Mechta-Grigoriou, Fatima
通讯作者：
Mechta-Grigoriou, Fatima