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多组学分析揭示了LAG3作为骨肉瘤预后和免疫生物标志物的潜力及其验证。

Multomic analysis reveals the potential of LAG3 as a prognostic and immune biomarker and its validation in osteosarcoma.

作者信息

Cao Qianqian, Zhang Yuzhe, Cheng Cheng, Wang Xiaoyang, Fan Panlong, Huang Jincheng, Dai Zhipeng

机构信息

Department of Orthopaedics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.

The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China.

出版信息

Sci Rep. 2025 Jul 11;15(1):25158. doi: 10.1038/s41598-025-10290-w.


DOI:10.1038/s41598-025-10290-w
PMID:40646089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12254381/
Abstract

Lymphocyte activation gene 3 (LAG3) is a member of the immunoglobulin superfamily and has been implicated in the development, growth, and progression of several cancers. However, the biological role of LAG3 has not been investigated in pan-cancer datasets. We sought to perform a comprehensive bioinformatics analysis of pan-cancer datasets to determine the relationship of LAG3 with patient survival prognosis, tumor microenvironment, immunotherapy responsiveness, and mechanisms regulating tumorigenesis. We used TCGA, GTEx, TIMER2, GDSC, CTRP, and TISCH databases and online websites to extract data on LAG3 in a variety of cancers, and analyzed pan-cancer patient datasets to explore not only the correlation between LAG3 expression and clinical stage, diagnosis, and prognosis of cancers, but also the correlation between LAG3 expression, gene variants, methylation status, tumor stemness, and tumor immunity. The biological functions of LAG3 in osteosarcoma cells were determined by in vitro CCK-8, wound healing and transwell assays. Finally, through in vivo experiments, the study preliminarily explored the impact of LAG3 on osteosarcoma and its correlation with immune genes. Pan-cancer analysis showed that LAG3 expression was up-regulated in a variety of cancers, and the expression of LAG3 was closely related to the clinical stage, diagnosis and prognosis of cancers. GO and KEGG enrichment analyses showed that LAG3 was enriched in inflammatory, metabolic, and immune signaling pathways in a variety of cancers. Meanwhile, LAG3 expression not only has an impact on patient immunotherapy prognosis and immunotherapy response, but also has a significant effect on drug sensitivity. In vitro experiments have shown that LAG3 promotes the proliferation, migration and invasion of osteosarcoma cells. In vivo xenotransplantation experiments further confirmed that LAG3 promotes the growth of osteosarcoma, and the expression of LAG3 is positively correlated with CD8, CD19, and CD68. Our study suggests that LAG3 is a promising marker for cancer diagnosis, prognosis, and treatment.

摘要

淋巴细胞激活基因3(LAG3)是免疫球蛋白超家族的成员,与多种癌症的发生、发展和进展有关。然而,尚未在泛癌数据集中研究LAG3的生物学作用。我们试图对泛癌数据集进行全面的生物信息学分析,以确定LAG3与患者生存预后、肿瘤微环境、免疫治疗反应性以及调节肿瘤发生的机制之间的关系。我们使用TCGA、GTEx、TIMER2、GDSC、CTRP和TISCH数据库及在线网站提取多种癌症中LAG3的数据,并分析泛癌患者数据集,不仅探索LAG3表达与癌症临床分期、诊断和预后之间的相关性,还探索LAG3表达、基因变异、甲基化状态、肿瘤干性和肿瘤免疫之间的相关性。通过体外CCK-8、伤口愈合和transwell实验确定LAG3在骨肉瘤细胞中的生物学功能。最后,通过体内实验,该研究初步探索了LAG3对骨肉瘤的影响及其与免疫基因的相关性。泛癌分析表明,LAG3在多种癌症中表达上调,且LAG3的表达与癌症的临床分期、诊断和预后密切相关。GO和KEGG富集分析表明,LAG3在多种癌症的炎症、代谢和免疫信号通路中富集。同时,LAG3表达不仅对患者免疫治疗预后和免疫治疗反应有影响,对药物敏感性也有显著作用。体外实验表明,LAG3促进骨肉瘤细胞的增殖、迁移和侵袭。体内异种移植实验进一步证实,LAG3促进骨肉瘤生长,且LAG3的表达与CD8、CD19和CD68呈正相关。我们的研究表明,LAG3是癌症诊断、预后和治疗的一个有前景的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/fd5d2f0a4509/41598_2025_10290_Fig16_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/fd5d2f0a4509/41598_2025_10290_Fig16_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/99379ab508a0/41598_2025_10290_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/55500876b4b1/41598_2025_10290_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/4659e2ffa3b8/41598_2025_10290_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/a63b99c5190c/41598_2025_10290_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/11bfe9b5818e/41598_2025_10290_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/740271d0842b/41598_2025_10290_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/ca4e377745ed/41598_2025_10290_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/57ef255fa8b3/41598_2025_10290_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/4feae0aab760/41598_2025_10290_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/5f0f578fc823/41598_2025_10290_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/f32059531782/41598_2025_10290_Fig14_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/221710792241/41598_2025_10290_Fig15_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/096f/12254381/fd5d2f0a4509/41598_2025_10290_Fig16_HTML.jpg

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