Deciphering KDM8 dysregulation and CpG methylation in hepatocellular carcinoma using multi-omics and machine learning.

IF 3 4区 医学 Q2 GENETICS & HEREDITY Epigenomics Pub Date : 2024-01-01 Epub Date: 2024-07-29 DOI:10.1080/17501911.2024.2374702
Firoz Ahmed, Nitish Kumar Mishra, Othman A Alghamdi, Mohammad Imran Khan, Aamir Ahmad, Nargis Khan, Mohammad Rehan
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Abstract

Aim: This study investigates the altered expression and CpG methylation patterns of histone demethylase KDM8 in hepatocellular carcinoma (HCC), aiming to uncover insights and promising diagnostics biomarkers.Materials & methods: Leveraging TCGA-LIHC multi-omics data, we employed R/Bioconductor libraries and Cytoscape to analyze and construct a gene correlation network, and LASSO regression to develop an HCC-predictive model.Results: In HCC, KDM8 downregulation is correlated with CpGs hypermethylation. Differential gene correlation analysis unveiled a liver carcinoma-associated network marked by increased cell division and compromised liver-specific functions. The LASSO regression identified a highly accurate HCC prediction signature, prominently featuring CpG methylation at cg02871891.Conclusion: Our study uncovers CpG hypermethylation at cg02871891, possibly influencing KDM8 downregulation in HCC, suggesting these as promising biomarkers and targets.

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利用多组学和机器学习破解肝细胞癌中的 KDM8 失调和 CpG 甲基化。
目的:本研究探讨了组蛋白去甲基化酶 KDM8 在肝细胞癌(HCC)中的表达和 CpG 甲基化模式的改变,旨在发现有价值的诊断生物标志物。材料与方法:利用TCGA-LIHC多组学数据,我们使用R/Bioconductor库和Cytoscape分析并构建了基因相关网络,并通过LASSO回归建立了HCC预测模型。结果在HCC中,KDM8下调与CpGs超甲基化相关。差异基因相关性分析揭示了一个肝癌相关网络,其特点是细胞分裂增加和肝脏特异性功能受损。LASSO 回归确定了一个高度准确的 HCC 预测特征,其显著特征是 cg02871891 处的 CpG 甲基化。结论我们的研究发现了 cg02871891 处的 CpG 高甲基化可能会影响 HCC 中 KDM8 的下调,这表明它们是很有前景的生物标记物和靶点。
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来源期刊
Epigenomics
Epigenomics GENETICS & HEREDITY-
CiteScore
5.80
自引率
2.60%
发文量
95
审稿时长
>12 weeks
期刊介绍: Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community. Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.
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