CDC25B 是一种与肝细胞癌免疫渗透和药物敏感性相关的预后生物标记物

Zixiang Huang, Liangzhi Xu, Zhengqiang Wu, Xiaofeng Xiong, Linfei Luo, Zhili Wen
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摘要

细胞分裂周期 25B(CDC25B)是 CDC25 磷酸酶家族的成员,在细胞周期调控中发挥着关键作用。研究表明,CDC25B 在多种癌症中具有致癌潜力,但 CDC25B 在肝细胞癌(HCC)发病中的作用仍鲜为人知。本研究的目的是利用生物信息学和实验阐明 CDC25B 在 HCC 中的作用。研究人员从癌症基因图谱(TCGA)和基因表达总库(GEO)数据库中获得了HCC癌组织和癌旁正常样本的CDC25B表达数据,并分析了CDC25B表达与HCC患者预后和肿瘤分化程度之间的关系。利用荧光定量聚合酶链反应(q-PCR)和蛋白免疫印迹(Western blot)技术验证了CDC25B在临床HCC组织样本中的表达。基因组富集分析(Gene set enrichment analysis,GSEA)用于鉴定富集 CDC25B 表达的信号通路,差异基因(DEGs)用于筛选共表达枢纽基因并构建蛋白-蛋白相互作用(PPI)网络。用5-乙炔基-2 ′-脱氧尿苷(EDU)染色比较了敲除CDC25B后HCC细胞系(HCC-LM3)的增殖和分化能力。最后,我们研究了CDC25B在HCC中的突变情况,以及CDC25B的表达与肿瘤细胞淋巴细胞浸润和一些免疫检查点以及药物敏感性之间的关系。CDC25B在HCC组织中过表达,并与HCC患者的不良预后和肿瘤分化程度相关。GSEA和PPI网络共同揭示了CDC25B过表达时与HCC发展相关的信号通路和功能的显著上调。EDU试验表明,在HCC-LM3s中下调CDC25B的表达后,细胞的分化增值能力明显降低。CDC25B 还参与了 HCC 中肿瘤微环境(TME)的形成和免疫过程,而且 CDC25B 的高表达会降低患者对某些药物的敏感性。CDC25B可作为HCC预后不良和部分药物敏感性的生物标志物和免疫治疗靶点,为HCC治疗提供新思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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CDC25B Is a Prognostic Biomarker Associated With Immune Infiltration and Drug Sensitivity in Hepatocellular Carcinoma

Cell division cycle 25B (CDC25B), a member of the CDC25 phosphatase family, plays a key role in cell cycle regulation. Studies have suggested its carcinogenic potential in various cancers, but the role of CDC25B in the development of hepatocellular carcinoma (HCC) remains poorly understood. The aim of this study was to clarify the role of CDC25B in HCC using bioinformatics and experiments. CDC25B expression data of HCC cancer tissues and paracancerous normal samples were obtained from The Cancer Gene Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the relationship between CDC25B expression and the prognosis and degree of tumor differentiation of HCC patients was analyzed. CDC25B expression was verified in clinical HCC tissue samples using fluorescence quantitative polymerase chain reaction (q-PCR) and protein immunoblotting (Western blot). Gene set enrichment analysis (GSEA) was used to identify signaling pathways enriched in CDC25B expression, and differential genes (DEGs) were used to screen out coexpressed hub genes and construct protein-protein interaction (PPI) networks. 5-Ethynyl-2 -deoxyuridine (EDU) staining was used to compare the proliferation and differentiation ability of the HCC cell line (HCC-LM3) after knockdown of CDC25B. Finally, we investigated the mutation of CDC25B in HCC and the relationship between CDC25B expression and tumor cell infiltration of lymphocytes and some immune checkpoints as well as drug sensitivity. CDC25B was overexpressed in HCC tissues and correlated with poor prognosis and the degree of tumor differentiation in patients with HCC. The GSEA and PPI networks together revealed significantly upregulated signaling pathways, as well as functions, associated with the development of HCC when CDC25B was overexpressed. The EDU assay demonstrated that the ability of cells to differentiate value addedly was markedly reduced following the downregulation of CDC25B expression in HCC-LM3s. CDC25B was also involved in the formation of the tumor microenvironment (TME) and immune processes in HCC, and the high expression of CDC25B made patients less sensitive to some drugs. CDC25B can be used as a biomarker and immunotherapeutic target for poor prognosis and partial drug sensitivity in HCC, providing new ideas for HCC treatment.

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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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