研究动态
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阐明m6A调节剂介导的肾上腺皮质癌甲基化修饰模式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.

发表日期:2023
作者: Wenhao Xu, Haoming Li, Yasir Hameed, Mostafa A Abdel-Maksoud, Saeedah Musaed Almutairi, Ayman Mubarak, Mohammed Aufy, Wael Alturaiki, Abdulaziz J Alshalani, Ayman M Mahmoud, Chen Li
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

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,会显著影响肿瘤患者的预后。然而,在肾上腺皮质癌(ACC)中,m6A调控剂如何影响肿瘤微环境(TME)细胞浸润以及如何影响ACC患者的预后尚不清楚。本研究评估了112例ACC患者的m6A改变模式,并探究了其与免疫浸润细胞特征之间的关联。我们采用非监督聚类方法对ACC患者的m6A改变模式进行分类,采用主成分分析(PCA)技术创建m6A评分,评估特定恶性肿瘤中的改变模式。我们发现ACC患者存在两种独立的m6A改变模式,TME细胞浸润特征与肿瘤免疫炎症和免疫贫血表型一致。m6A评分也作为ACC患者的独立预测因子。通过m6A改变模式可以预测染色体体细胞数变异(CNV)和患者的预后。此外,m6A评分高的ACC患者具有更好的总生存率(OS)和免疫检查点阻断治疗更高的效率。我们的研究证明了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ACC患者预后预测和免疫治疗选择。© 2023 Xu等。
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.© 2023 Xu et al.