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CDC25B是一种与肝细胞癌免疫浸润和药物敏感性相关的预后生物标志物。

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

作者信息

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

机构信息

Department of Gastroenterology The Second Affiliated Hospital of Jiangxi Medical College Nanchang University, Nanchang, China.

Department of Hepatobiliary Surgery Ezhou Central Hospital, Ezhou, Hubei, China.

出版信息

Int J Genomics. 2024 Sep 28;2024:8922878. doi: 10.1155/2024/8922878. eCollection 2024.

Abstract

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.

摘要

细胞分裂周期25B(CDC25B)是CDC25磷酸酶家族的成员,在细胞周期调控中起关键作用。研究表明其在多种癌症中具有致癌潜力,但CDC25B在肝细胞癌(HCC)发生发展中的作用仍知之甚少。本研究旨在通过生物信息学和实验阐明CDC25B在HCC中的作用。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获取HCC癌组织和癌旁正常样本的CDC25B表达数据,并分析CDC25B表达与HCC患者预后及肿瘤分化程度的关系。采用荧光定量聚合酶链反应(q-PCR)和蛋白质免疫印迹法(Western blot)在临床HCC组织样本中验证CDC25B表达。利用基因集富集分析(GSEA)确定在CDC25B表达中富集的信号通路,并使用差异基因(DEG)筛选共表达的枢纽基因并构建蛋白质-蛋白质相互作用(PPI)网络。采用5-乙炔基-2'-脱氧尿苷(EDU)染色比较敲低CDC25B后HCC细胞系(HCC-LM3)的增殖和分化能力。最后,我们研究了HCC中CDC25B的突变情况以及CDC25B表达与淋巴细胞肿瘤细胞浸润、一些免疫检查点和药物敏感性之间的关系。CDC25B在HCC组织中过表达,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,当CDC25B过表达时,与HCC发生发展相关的信号通路以及功能显著上调。EDU检测表明,下调HCC-LM3s中CDC25B表达后,细胞的增值分化能力明显降低。CDC25B还参与了HCC肿瘤微环境(TME)的形成和免疫过程,CDC25B的高表达使患者对某些药物不太敏感。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd9a/11455594/9eab64dd43a7/IJG2024-8922878.001.jpg

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