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在泛癌中利用综合单细胞和批量测序研究[具体内容缺失]在肿瘤微环境及免疫治疗中的作用。

The role of in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

作者信息

Wu Guang-Hao, He Chao, Che Gang, Zhou Zheng, Chen Bi-Ying, Wu Hai-Ming, Chen Jian-Feng, Zhu Wei-Pu, Yang Yan, Zhou Zhan, Teng Li-Song, Wang Hai-Yong

机构信息

School of Clinical Medicine, Hangzhou Normal University Medical College, Hangzhou, China.

Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Heliyon. 2024 May 1;10(9):e30505. doi: 10.1016/j.heliyon.2024.e30505. eCollection 2024 May 15.

DOI:10.1016/j.heliyon.2024.e30505
PMID:38726194
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11079299/
Abstract

has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of within TME. Furthermore, we determined the expression levels of in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that , in particular, exhibited elevated expression levels within tumor tissues and co-expressed with in CAFs based on the multiplex immunofluorescence staining results.

摘要

已被确定为整合素连接激酶信号通路的参与者,影响上皮-间质转化,从而影响肿瘤的起始、进展和侵袭。而其在肿瘤微环境(TME)中的特征及其对免疫治疗的影响仍不清楚。因此,我们进行了全面分析,使用Kaplan-Meier分析来评估其预后意义。此外,我们采用富集分析来揭示潜在的分子机制。使用“Immunedeconv”软件包,我们评估了TME中其免疫特征。此外,我们根据单细胞测序数据确定了TME中各种细胞类型中其的表达水平。为了证实其与癌症相关成纤维细胞(CAF)标志物的共表达,我们对多种癌症类型的组织石蜡切片进行了多重免疫荧光染色。我们的分析揭示了在特定癌症类型中其表达升高与不良预后之间存在显著相关性。此外,我们发现其表达与多种免疫相关因素之间存在密切相关性,包括免疫检查点分子、免疫细胞浸润、微卫星不稳定性(MSI)和肿瘤突变负荷(TMB)。此外,FERMT2表达与免疫相关通路之间存在显著相关性,特别是那些与多种癌症类型中激活、迁移和促进成纤维细胞生长相关的通路。有趣的是,我们观察到其在恶性肿瘤细胞和基质细胞中均有一致的共表达,特别是在CAF中。值得注意的是,我们的研究结果还表明,特别是基于多重免疫荧光染色结果,其在肿瘤组织中表达水平升高,并与CAF中的 共表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/4702634bb135/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/b8f3bdb2e3f8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/c7fc80c7ea45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/1dc81d8a32ea/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/1b2ea137a8de/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/18b40230f275/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/528dea9111bd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/d6892c4b5c81/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/4702634bb135/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/b8f3bdb2e3f8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/c7fc80c7ea45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/1dc81d8a32ea/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/1b2ea137a8de/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/18b40230f275/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/528dea9111bd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/d6892c4b5c81/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ea/11079299/4702634bb135/gr8.jpg

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本文引用的文献

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FERMT2 upregulation in CAFs enhances EMT of OSCC and M2 macrophage polarization.癌相关成纤维细胞中FERMT2的上调增强了口腔鳞状细胞癌的上皮-间质转化和M2巨噬细胞极化。
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YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8 T cells.
YTHDF2 通过 CD8 T 细胞协调肿瘤相关巨噬细胞重编程并控制抗肿瘤免疫。
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Alzheimer's risk factor FERMT2 promotes the progression of colorectal carcinoma via Wnt/β-catenin signaling pathway and contributes to the negative correlation between Alzheimer and cancer.阿尔茨海默病风险因子 FERMT2 通过 Wnt/β-连环蛋白信号通路促进结直肠癌的进展,并导致阿尔茨海默病和癌症之间的负相关。
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