m6A RNA 甲基化调节因子在 HBV 相关肝细胞癌的诊断和亚型分类中的意义。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI:10.1007/s13577-024-01044-3
Qijuan Zang, Yalin Ju, Siyi Liu, Shaobo Wu, Chengbin Zhu, Liangru Liu, Weicheng Xu, Yingli He
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引用次数: 0

摘要

近年来,肝细胞癌(HCC)中 m6A 的异常改变一直是研究其生物学意义的重点。在本研究中,我们的目的是确定 m6A 修饰是否会导致 HBV 相关 HCC 的进展。为此,我们采用随机森林模型从 19 个候选基因中筛选出前 8 个特征性 m6A 调节因子。随后,我们建立了一个提名图模型,利用这 8 个特征性 m6A 调节因子来预测 HBV 相关 HCC 的患病率。根据决策曲线分析,患者可从提名图模型中获益。临床影响曲线显示了提名图模型强大的预测能力。此外,还采用了共识分子亚型分析来确定 m6A 修饰模式和 m6A 相关基因特征。免疫细胞亚群的量化是通过实施 ssGSEA 算法完成的。开发了 PCA 算法来计算单个肿瘤的 m6A 分数。两种不同的m6A修饰模式,即群组A和群组B,与不同的免疫浸润模式和生物通路表现出显著的相关性。值得注意的是,根据 m6A 评分标准,与 A 组患者相比,B 组患者的 m6A 评分更高。此外,通过免疫荧光验证了 IGFBP3 蛋白的表达,发现它们在肿瘤组织中的表达明显较低。总之,我们的研究强调了 m6A 修饰在 HBV 相关 HCC 进展中的重要性。这项研究有可能为鉴定 HBV 相关 HCC 提供新的预后生物标志物和治疗靶点。
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The significance of m6A RNA methylation regulators in diagnosis and subtype classification of HBV-related hepatocellular carcinoma.

In recent years, abnormal m6A alteration in hepatocellular carcinoma (HCC) has been a focus on investigating the biological implications. In this study, our objective is to determine whether m6A modification contributes to the progression of HBV-related HCC. To achieve this, we employed a random forest model to screen top 8 characteristic m6A regulators from 19 candidate genes. Subsequently, we developed a nomogram model that utilizes these 8 characteristic m6A regulators to predict the prevalence of HBV-related HCC. According to decision curve analysis, patients may benefit from the nomogram model. The clinical impact curves exhibited a robust predictive capability of the nomogram models. Additionally, consensus molecular subtyping was employed to identify m6A modification patterns and m6A-related gene signature. The quantification of immune cell subsets was accomplished through the implementation of ssGSEA algorithms. PCA algorithms were developed to compute the m6A score for individual tumors. Two distinct m6A modification patterns, namely cluster A and cluster B, exhibited significant correlations with distinct immune infiltration patterns and biological pathways. Notably, patients belonging to cluster B demonstrated higher m6A scores compared to those in cluster A, as determined by the m6A score metric. Furthermore, the expression of IGFBP3 proteins was validated through immunofluorescence, revealing their pronounced lower expression in tumor tissues. In summary, our study underscores the importance of m6A modification in the advancement of HBV-related HCC. This research has the potential to yield novel prognostic biomarkers and therapeutic targets for the identification of HBV-related HCC.

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4.30%
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567
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