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鉴定肝癌五个关键区域的四种关键组蛋白修饰共同调控的靶基因。

Identification of target genes co-regulated by four key histone modifications of five key regions in hepatocellular carcinoma.

机构信息

School of Artificial Intelligence, Anhui University of Science and Technology, Huainan 232001, China.

School of Artificial Intelligence, Anhui University of Science and Technology, Huainan 232001, China.

出版信息

Methods. 2024 Nov;231:165-177. doi: 10.1016/j.ymeth.2024.09.017. Epub 2024 Sep 28.

DOI:10.1016/j.ymeth.2024.09.017
PMID:39349287
Abstract

Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. Studies have shown that histone modification plays an important regulatory role in the occurrence and development of HCC. However, the specific regulatory effects of histone modifications on gene expression in HCC are still unclear. This study focuses on HepG2 cell lines and hepatocyte cell lines. First, the distribution of histone modification signals in the two cell lines was calculated and analyzed. Then, using the random forest algorithm, we analyzed the effects of different histone modifications and their modified regions on gene expression in the two cell lines, four key histone modifications (H3K36me3, H3K4me3, H3K79me2, and H3K9ac) and five key regions that co-regulate gene expression were obtained. Subsequently, target genes regulated by key histone modifications in key regions were screened. Combined with clinical data, Cox regression analysis and Kaplan-Meier survival analysis were performed on the target genes, and four key target genes (CBX2, CEBPZOS, LDHA, and UMPS) related to prognosis were identified. Finally, through immune infiltration analysis and drug sensitivity analysis of key target genes, the potential role of key target genes in HCC was confirmed. Our results provide a theoretical basis for exploring the occurrence of HCC and propose potential biomarkers associated with histone modifications, which may be potential drug targets for the clinical treatment of HCC.

摘要

肝细胞癌(HCC)是一种发病率和死亡率都很高的癌症。研究表明,组蛋白修饰在 HCC 的发生和发展中起着重要的调节作用。然而,组蛋白修饰对 HCC 中基因表达的具体调节作用仍不清楚。本研究聚焦于 HepG2 细胞系和肝细胞系。首先,计算和分析了这两种细胞系中组蛋白修饰信号的分布。然后,使用随机森林算法,分析了不同组蛋白修饰及其修饰区域对两种细胞系中基因表达的影响,得到了四个关键的组蛋白修饰(H3K36me3、H3K4me3、H3K79me2 和 H3K9ac)和五个共同调节基因表达的关键区域。随后,筛选了关键区域中关键组蛋白修饰调节的靶基因。结合临床数据,对靶基因进行 Cox 回归分析和 Kaplan-Meier 生存分析,鉴定出四个与预后相关的关键靶基因(CBX2、CEBPZOS、LDHA 和 UMPS)。最后,通过关键靶基因的免疫浸润分析和药物敏感性分析,验证了关键靶基因在 HCC 中的潜在作用。我们的研究结果为探索 HCC 的发生提供了理论依据,并提出了与组蛋白修饰相关的潜在生物标志物,这些标志物可能是 HCC 临床治疗的潜在药物靶点。

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