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FAM210B 在肝细胞癌中的多效性作用:对肿瘤进展、微环境调节和治疗选择的影响。

Multifaceted role of FAM210B in hepatocellular carcinoma: Implications for tumour progression, microenvironment modulation and therapeutic selection.

机构信息

Department of Pathology and Pathophysiology, School of Basic Medicine, Anhui Medical College, Hefei, China.

出版信息

J Cell Mol Med. 2024 Aug;28(16):e70031. doi: 10.1111/jcmm.70031.

DOI:10.1111/jcmm.70031
PMID:39198940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11358035/
Abstract

Hepatocellular carcinoma (HCC) is a common and lethal liver cancer characterized by complex aetiology and limited treatment options. FAM210B, implicated in various cancers, is noteworthy for its potential role in the progression and treatment response of HCC. Yet, its expression patterns, functional impacts and correlations with patient outcomes and resistance to therapy are not well understood. We employed a comprehensive methodology to explore the role of FAM210B in HCC, analysing its expression across cancers, subcellular localization and impacts on cell proliferation, invasion, migration, biological enrichment and the immune microenvironment. Additionally, we investigated its expression in single cells, drug sensitivity and relationships with genomic instability, immunotherapy efficacy and key immune checkpoints. While FAM210B expression varied across cancers, there was no notable difference between HCC and normal tissues. Elevated levels of FAM210B were associated with improved survival outcomes. Subcellular analysis located FAM210B in the plasma membrane and cytosol. FAM210B was generally downregulated in HCC, and its suppression significantly enhanced cell proliferation, invasion and migration. Biological enrichment analysis linked FAM210B to metabolic and immune response pathways. Moreover, its expression modified the immune microenvironment of HCC, affecting drug responsiveness and immunotherapy outcomes. High expression levels of FAM202B correlated with increased resistance to sunitinib and enhanced responsiveness to immunotherapy, as evidenced by associations with tumour mutation burden, PDCD1, CTLA4 and TIDE scores. FAM210B exerts a complex influence on HCC, affecting tumour cell behaviour, metabolic pathways, the immune microenvironment and responses to therapy.

摘要

肝细胞癌(HCC)是一种常见且致命的肝癌,其病因复杂,治疗选择有限。FAM210B 与多种癌症有关,其在 HCC 的进展和治疗反应中的潜在作用值得关注。然而,其表达模式、功能影响以及与患者预后和对治疗的耐药性的相关性尚不清楚。我们采用了一种全面的方法来研究 FAM210B 在 HCC 中的作用,分析了其在癌症中的表达、亚细胞定位以及对细胞增殖、侵袭、迁移、生物学富集和免疫微环境的影响。此外,我们还研究了其在单细胞中的表达、药物敏感性以及与基因组不稳定性、免疫治疗疗效和关键免疫检查点的关系。虽然 FAM210B 的表达在各种癌症中有所不同,但在 HCC 与正常组织之间没有明显差异。FAM210B 水平升高与生存结局改善相关。亚细胞分析将 FAM210B 定位在质膜和细胞质中。FAM210B 在 HCC 中通常下调,其抑制显著增强了细胞增殖、侵袭和迁移。生物学富集分析将 FAM210B 与代谢和免疫反应途径联系起来。此外,其表达改变了 HCC 的免疫微环境,影响了药物反应性和免疫治疗结果。FAM202B 的高表达水平与对舒尼替尼的耐药性增加和对免疫治疗的反应性增强相关,这与肿瘤突变负担、PDCD1、CTLA4 和 TIDE 评分有关。FAM210B 对 HCC 有复杂的影响,影响肿瘤细胞行为、代谢途径、免疫微环境以及对治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/7d5c84404e47/JCMM-28-e70031-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/844b576f0408/JCMM-28-e70031-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/1599cbe41ada/JCMM-28-e70031-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/10c8f682fbd2/JCMM-28-e70031-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/15238e63c4ad/JCMM-28-e70031-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/7d5c84404e47/JCMM-28-e70031-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/844b576f0408/JCMM-28-e70031-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/1c2c2747bb6b/JCMM-28-e70031-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/7b1670f8f7c3/JCMM-28-e70031-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/1599cbe41ada/JCMM-28-e70031-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/b14a734ae1fa/JCMM-28-e70031-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/10c8f682fbd2/JCMM-28-e70031-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/15238e63c4ad/JCMM-28-e70031-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d70/11358035/7d5c84404e47/JCMM-28-e70031-g008.jpg

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本文引用的文献

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Cell Biochem Funct. 2024 Jan;42(1):e3913. doi: 10.1002/cbf.3913.
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Hypoxia-driven tumor stromal remodeling and immunosuppressive microenvironment in scirrhous HCC.缺氧驱动的硬癌型 HCC 肿瘤基质重构和免疫抑制微环境
Hepatology. 2024 Apr 1;79(4):780-797. doi: 10.1097/HEP.0000000000000599. Epub 2023 Sep 19.
3
Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma.
新型线粒体膜蛋白FAM210B的缺失与肝细胞癌相关。
Biomedicines. 2023 Apr 21;11(4):1232. doi: 10.3390/biomedicines11041232.
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Breakthroughs in Hepatocellular Carcinoma Therapies.肝细胞癌治疗的突破。
Clin Gastroenterol Hepatol. 2023 Jul;21(8):2135-2149. doi: 10.1016/j.cgh.2023.01.039. Epub 2023 Feb 20.
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Safety and Efficacy of Robotic vs Open Liver Resection for Hepatocellular Carcinoma.机器人与开放式肝切除术治疗肝细胞癌的安全性和疗效。
JAMA Surg. 2023 Jan 1;158(1):46-54. doi: 10.1001/jamasurg.2022.5697.
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Elucidation of the Role of FAM210B in Mitochondrial Metabolism and Erythropoiesis.阐明 FAM210B 在线粒体代谢和红细胞生成中的作用。
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