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综合分析和实验确定膜联蛋白A1(ANXA1)是神经胶质瘤预后不良的指标。

Comprehensive analysis and experiments identified ANXA1 as an unfavorable prognosticator in glioma.

作者信息

Fan Yu, Chen Yanwen, Run Xingda, Qiu Huaide, Hu Qianxing, Zhao Xudong, Bao ZhongYuan, Miao Zengli

机构信息

Department of neurosurgery, Jiangnan university Medical Center, Wuxi, Jiangsu province, 214002, PR China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu province, 214002, PR China.

Faculty of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing, 210023, China.

出版信息

Transl Oncol. 2025 Mar;53:102286. doi: 10.1016/j.tranon.2025.102286. Epub 2025 Jan 21.

DOI:10.1016/j.tranon.2025.102286
PMID:39842212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11791432/
Abstract

BACKGROUND

ANXA1 was upregulated in gliomas in previous bulk sequencing studies. we examined the role of ANXA1 in glioma using bioinformatics analysis and experiments.

METHODS

Two cohorts were adopted to validate the prognostic value of ANXA1 in gliomas. Real-time quantitative PCR and western blotting were performed on samples for further validation. Using the data of GSE162631, ANXA1 expression was analyzed in different cells in glioblastoma specimen. In different groups, lentiviral vector or the empty vector was used to construct cell lines. Wound-healing assay, along with Transwell assay, was conducted to assess the migration and invasion of glioma cells. Animal studies were conducted to examine the role of ANXA1 in gliomas.

RESULTS

ANXA1 expression was associated with overall survival in glioma patients. In glioblastomas, ANXA1 expression was higher than in low-grade gliomas. Among patients receiving chemo- or radiotherapy, high ANXA1 expression presented a shorter overall survival. Single-cell sequencing showed that ANXA1 was expressed in a higher proportion and level in glioblastomas cells than in normal cells; whereas, ANXA1 was enriched in T cells among immune cells. As shown in experiments, knockdown of ANXA1 could attenuate the proliferation, migration and invasion of glioma cells in vitro and vivo, thereby improving the prognosis of animals.

CONCLUSIONS

ANXA1 can promote the proliferation, migration and invasion of glioma; its expression is positively correlated with immune response and poor prognosis of glioma. The cancer-promoting mechanisms of ANXA1 in glioma and its correlation with the functional status of glioma patients warrant further investigation.

摘要

背景

在先前的批量测序研究中,膜联蛋白A1(ANXA1)在胶质瘤中上调。我们使用生物信息学分析和实验研究了ANXA1在胶质瘤中的作用。

方法

采用两个队列来验证ANXA1在胶质瘤中的预后价值。对样本进行实时定量PCR和蛋白质免疫印迹法以进一步验证。利用GSE162631的数据,分析胶质母细胞瘤标本中不同细胞的ANXA1表达。在不同组中,使用慢病毒载体或空载体构建细胞系。进行伤口愈合试验以及Transwell试验以评估胶质瘤细胞的迁移和侵袭。开展动物研究以考察ANXA1在胶质瘤中的作用。

结果

ANXA1表达与胶质瘤患者的总生存期相关。在胶质母细胞瘤中,ANXA1表达高于低级别胶质瘤。在接受化疗或放疗的患者中,ANXA1高表达者总生存期较短。单细胞测序显示,胶质母细胞瘤细胞中ANXA1的表达比例和水平高于正常细胞;而在免疫细胞中,ANXA1在T细胞中富集。实验表明,敲低ANXA1可在体外和体内减弱胶质瘤细胞的增殖、迁移和侵袭,从而改善动物预后。

结论

ANXA1可促进胶质瘤的增殖、迁移和侵袭;其表达与胶质瘤的免疫反应及不良预后呈正相关。ANXA1在胶质瘤中的促癌机制及其与胶质瘤患者功能状态的相关性值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/56347b73f280/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/a6abd278ed7c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/7970abfc7cbb/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/97d6dcbb8056/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/c8cbe626c6a7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/0622715faa50/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/24fe626f588d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/56347b73f280/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/a6abd278ed7c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/7970abfc7cbb/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/97d6dcbb8056/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/c8cbe626c6a7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/0622715faa50/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/24fe626f588d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebbc/11791432/56347b73f280/gr7.jpg

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J Immunother Cancer. 2024 Sep 4;12(9):e009318. doi: 10.1136/jitc-2024-009318.
2
Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment.胶质瘤来源的膜联蛋白A1通过促进抗炎性肿瘤微环境来抑制对Toll样受体3配体的免疫反应。
Cell Mol Immunol. 2024 Jan;21(1):47-59. doi: 10.1038/s41423-023-01110-0. Epub 2023 Dec 4.
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ANXA1 Promotes Tumor Immune Evasion by Binding PARP1 and Upregulating Stat3-Induced Expression of PD-L1 in Multiple Cancers.
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Cancer Immunol Res. 2023 Oct 4;11(10):1367-1383. doi: 10.1158/2326-6066.CIR-22-0896.
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Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.脑胶质瘤中肿瘤与免疫微环境的自然协同进化。
Cancer Discov. 2022 Dec 2;12(12):2820-2837. doi: 10.1158/2159-8290.CD-22-0196.
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