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多种表观遗传修饰谱揭示了葡萄膜黑色素瘤的肿瘤免疫微环境和临床结局。

Multiple epigenetic modification profiles reveal the tumor immune microenvironment and clinical outcomes of uveal melanoma.

作者信息

Nan Xinshuai, Liu Yuchen, Gao Yuzhen, Nan Xinshan

机构信息

Department of Ophthalmology, Subei Peoples' Hospital Affiliated to Yangzhou University, Yangzhou, China.

Department of Ophthalmology, Yangzhou Aier New Vision Eye Hospital, Yangzhou, China.

出版信息

Front Genet. 2023 Apr 12;14:1155199. doi: 10.3389/fgene.2023.1155199. eCollection 2023.

DOI:10.3389/fgene.2023.1155199
PMID:37124608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10132731/
Abstract

Uveal melanoma (UM) is an aggressive intraocular cancer that, in 50% of cases, spreads to the patient's other systems. The exact cause of the increased metastatic rate is still unknown. Methylation and immune response, metastasis, and the expansion of cancer cells are closely related. Additionally, proteins linked to RNA methylation have come to light as possible cancer treatment targets. However, the relationship between methylation-related genes (MRGs) and the tumor microenvironment (TME) is still not understood. The goal of this work was to discover important MRGs and create a signature for UM patients' prognosis prediction. Using two different data sets, we examined the MRG expression patterns in the transcriptional and genomic regions of 106 UM samples. We discovered a connection between the clinicopathological traits of the patients, their prognosis, the capability of TME cells to infiltrate, and various MRG changes. Following that, we developed an MRGs signature to forecast prognosis, and we evaluated the model's precision in patients with UM. We grouped the patients into multiple categories based on their clinical traits, looked at the survival rates for various groups within various groupings, and tested their accuracy. Additionally, to increase the practical usability of the MRGs model, we created a very accurate nomogram. TIDE scores were higher in the low-risk group. We go over how MGRs could impact UM's TME, immunotherapy responsiveness, prognosis, and clinically significant features. We looked for different chemotherapeutic drugs and cutting-edge targeted agents for patients in diverse subgroups in order to better understand MRGs in UM. This helped in the creation of customized therapy to open new doors. We could also further research the prognosis and develop more efficient immunotherapy regimens.

摘要

葡萄膜黑色素瘤(UM)是一种侵袭性眼内癌,在50%的病例中会扩散到患者的其他系统。转移率增加的确切原因仍然未知。甲基化与免疫反应、转移以及癌细胞的扩增密切相关。此外,与RNA甲基化相关的蛋白质已成为可能的癌症治疗靶点。然而,甲基化相关基因(MRGs)与肿瘤微环境(TME)之间的关系仍不清楚。这项工作的目标是发现重要的MRGs,并创建一个用于预测UM患者预后的特征。使用两个不同的数据集,我们检查了106个UM样本的转录和基因组区域中的MRG表达模式。我们发现了患者的临床病理特征、预后、TME细胞浸润能力以及各种MRG变化之间的联系。随后,我们开发了一个MRGs特征来预测预后,并评估了该模型在UM患者中的准确性。我们根据患者的临床特征将他们分为多个类别,查看不同分组中各个组别的生存率,并测试其准确性。此外,为了提高MRGs模型的实际可用性,我们创建了一个非常准确的列线图。低风险组的TIDE评分更高。我们探讨了MGRs如何影响UM的TME、免疫治疗反应性、预后和临床显著特征。我们为不同亚组的患者寻找不同的化疗药物和前沿靶向药物,以便更好地了解UM中的MRGs。这有助于创建定制治疗方案,打开新的局面。我们还可以进一步研究预后,并开发更有效的免疫治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/03383e13cb6c/fgene-14-1155199-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/e9e2f4317081/fgene-14-1155199-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/95f5ab3aa709/fgene-14-1155199-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/94fd4cfd3a13/fgene-14-1155199-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/c266a11ac336/fgene-14-1155199-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/3ecbff39ebfd/fgene-14-1155199-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/03383e13cb6c/fgene-14-1155199-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/e9e2f4317081/fgene-14-1155199-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/95f5ab3aa709/fgene-14-1155199-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/94fd4cfd3a13/fgene-14-1155199-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/c266a11ac336/fgene-14-1155199-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/3ecbff39ebfd/fgene-14-1155199-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/10132731/03383e13cb6c/fgene-14-1155199-g007.jpg

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