FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma.
FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma.
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FGL1 作为恶性透明细胞肾细胞癌进展的新型介质和标记物
DOI：
10.3389/fonc.2021.756843
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Lv Z;Cui B;Huang X;Feng HY;Wang T;Wang HF;Xuan YD;Li HZ;Ma X;Huang Y;Zhang X
透明细胞肾细胞癌（ccRCC）是最常见的肾细胞癌亚型，预后较差。目前正在研究增强 ccRCC 治疗中免疫反应的新兴策略。纤维蛋白原样蛋白 1 (FGL1) 是肿瘤可能通过结合 LAG-3 和负调节 T 细胞来逃避免疫系统的一种新机制。在本研究中，我们旨在探讨 FGL1 在 ccRCC 中的潜在机制及其表达和预后价值。我们发现 FGL1 在 ccRCC 患者的肿瘤组织和血浆标本中表达上调。 FGL1 高表达预示着 ccRCC 患者预后不良。我们还发现，FGL1 的过度表达通过激活上皮间质转化 (EMT) 来增强 RCC 细胞的迁移、侵袭和转移。与这些结果一致，我们通过组织微阵列分析发现 FGL1 和 EMT 相关基因的表达之间存在显着的正相关性。基因表达分析显示，FGL1 缺陷的 ccRCC 细胞系改变了炎症反应、细胞间信号传导、T 细胞激活的负调节和细胞内信号转导的转录输出。在原位异种移植小鼠模型中，FGL1 的缺失显着抑制肿瘤生长和肺转移。当 FGL1 表达减少时，肿瘤微环境 (TME) 中骨髓源性 CD11b+ 和 Ly6G+ 免疫细胞的浸润显着减少。因此，ccRCC中FGL1表达增加与不良预后呈正相关。从机制上讲，FGL1 促进 EMT 过程并调节 TME，从而促进 ccRCC 进展和转移。因此，靶向 FGL1 可能会改善 ccRCC 患者的临床结果。
Clear cell renal cell carcinoma (ccRCC), which is the most prevalent renal cell carcinoma subtype, has a poor prognosis. Emerging strategies for enhancing the immune response in ccRCC therapy are currently being investigated. Fibrinogen-like Protein 1(FGL1) is a novel mechanism that tumors may use to evade the immune system by binding LAG-3 and negatively regulating T cells. In this study, we aimed at investigating the underlying mechanism of FGL1 in ccRCC, and its expression and prognostic value. We found that FGL1 was upregulated in tumor tissues and plasma specimens of ccRCC patients. High FGL1 expression predicted a poor prognosis for ccRCC patients. We also discovered that overexpression of FGL1 enhances RCC cell migration, invasion, and metastasis by activating the epithelial-to-mesenchymal transition (EMT). Consistent with these results, we identified a significant positive correlation between expression of FGL1 and EMT-related genes through tissue microarray analysis. Gene-expression analysis revealed that FGL1-deficient ccRCC cell lines had altered transcriptional output in inflammatory response, cell-cell signaling, negative regulation of T cell activation, and intracellular signal transduction. Depletion of FGL1 significantly inhibited tumor growth and lung metastasis in orthotopic xenograft mouse model. Infiltration of myeloid-derived CD11b+ and Ly6G+ immune cells in tumor microenvironment (TME) was strikingly decreased when FGL1 expression reduced. Therefore, increased FGL1 expression in ccRCC is positively correlated with poor prognosis. Mechanistically, FGL1 facilitates the EMT process and modulates TME, which promotes ccRCC progression and metastasis. Consequently, targeting FGL1 can potentially improve clinical outcome of ccRCC patients.
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内皮δ样4（DLL4）促进肾细胞癌血行转移
影响因子：
--
作者：
Huang QB;Ma X;Li HZ;Ai Q;Liu SW;Zhang Y;Gao Y;Fan Y;Ni D;Wang BJ;Zhang X
通讯作者：
Zhang X
影响因子：
4.1
作者：
Jung, Tae Woo;Chung, Yoon Hee;Jeong, Ji Hoon
通讯作者：
Jeong, Ji Hoon
影响因子：
45.3
作者：
Motzer, Robert J.;Barrios, Carlos H.;Knox, Jennifer J.
通讯作者：
Knox, Jennifer J.
影响因子：
24.5
作者：
Li, Chang-Yan;Cao, Chuan-Zeng;Yang, Xiao-Ming
通讯作者：
Yang, Xiao-Ming
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators