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阐明 m6A 调节剂介导的甲基化修饰模式在肾上腺皮质癌中的临床和免疫学价值。

Elucidating the clinical and immunological value of m6A regulator-mediated methylation modification patterns in adrenocortical carcinoma.

机构信息

Department of Urology, Urological Surgery Research Institute, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Department of Urology, Affiliated Hospital of Guilin Medical University, Guilin, China.

出版信息

Oncol Res. 2023 Jul 21;31(5):819-831. doi: 10.32604/or.2023.029414. eCollection 2023.

Abstract

N6-methyladenosine methylation (m6A) is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients. However, it is unknown how the m6A regulator affects the tumor microenvironment (TME) cell infiltration in adrenocortical carcinoma (ACC) and how it affects the prognosis of ACC patients yet. The m6A alteration patterns of 112 ACC patients were evaluated, furthermore, the association with immune infiltration cell features was investigated. The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients. The principal component analysis (PCA) technique was taken to create the m6A score to assess the alteration pattern in specific malignancies. We found two independent patterns of m6A alteration in ACC patients. The TME cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both patterns. The m6Ascore also served as an independent predictive factor in ACC patients. The somatic copy number variation (CNV) and patients prognosis can be predicted by m6A alteration patterns. Moreover, the ACC patients with high m6A scores had better overall survival (OS) and higher efficiency in immune checkpoint blockade therapy. Our work demonstrated the significance of m6A alteration to the ACC patients immunotherapy. The individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice.

摘要

N6-甲基腺苷甲基化(m6A)是一种常见的表观遗传改变类型,它对肿瘤患者的预后有显著影响。然而,目前尚不清楚 m6A 调节剂如何影响肾上腺皮质癌(ACC)中的肿瘤微环境(TME)细胞浸润,以及它如何影响 ACC 患者的预后。评估了 112 名 ACC 患者的 m6A 改变模式,并进一步研究了其与免疫浸润细胞特征的关联。采用无监督聚类方法对 ACC 患者的 m6A 改变模式进行分类。采用主成分分析(PCA)技术构建 m6A 评分,以评估特定恶性肿瘤中的改变模式。我们发现 ACC 患者中存在两种独立的 m6A 改变模式。两种模式的 TME 细胞浸润特征与肿瘤免疫炎症和免疫荒漠表型均显著一致。m6A 评分也是 ACC 患者的独立预测因素。m6A 改变模式可以预测肿瘤的体细胞拷贝数变异(CNV)和患者的预后。此外,m6A 评分高的 ACC 患者的总生存期(OS)更好,免疫检查点阻断治疗的效率更高。我们的工作表明 m6A 改变对 ACC 患者免疫治疗的重要性。个体 m6A 改变模式分析可能有助于预测 ACC 患者的预后和免疫治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a457/10398396/fca24e644761/OncolRes-31-29414-f001.jpg

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