基于GSEA分析FoxM1表达变化对人肝内胆管细胞癌增殖及侵袭相关信号通路的影响

doi:10.20047/j.issn1673-7210.2022.29.04

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摘要目的通过比较分析FoxM1表达高低对肝内胆管细胞癌（ICC）中增殖及侵袭相关细胞信号通路的影响，进而部分揭示其发生发展分子机制。方法从TCGA数据库下载36例ICC患者的mRNA数据，按照总体叉头盒蛋白M1（FoxM1）表达值中位数将其分为FoxM1高表达组、FoxM1低表达组，使用基因集富集分析（GSEA）软件进行生物信息学分析寻找FoxM1高低表达组之间可能存在的差异表达基因及影响的相关信号通路。采用实时荧光定量PCR（RT-PCR）比较ICC细胞系中FoxM1及P53 mRNA的表达关系。结果 GSEA分析表明，ICC中FoxM1高表达组中常见基因信号通路如P53、MYC信号通路表达差异均有统计学意义，而FoxM1低表达组中FOXO等信号通路表达差异有统计学意义（均FDR-q值＜ 0.250）。RT-PCR结果显示，慢病毒转染后上调FoxM1表达的HCCC-9810-FoxM1细胞组中P53 mRNA表达较对照组升高，而下调FoxM1表达的SSP-25-shFoxM1细胞组中P53 mRNA水平较对照组则下降，差异均有统计学意义（P ＜ 0.000 1）。结论 FoxM1可能在ICC发生发展等不同演进阶段产生广泛作用。FoxM1表达可能与P53相关，ICC中FoxM1可能影响P53信号通路。

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	刘凌云* 毛涵* 黄培露陈书乐

关键词 ：叉头盒蛋白M1, 肝内胆管细胞癌, 增殖, 信号通路, 计算生物学, P53

Abstract：Objective To compare and analyze the effects of FoxM1 expression on the proliferation and invasion-related cell signaling pathways in intrahepatic cholangiocarcinoma (ICC), and to reveal the molecular mechanism of its occurrence and development. Methods The mRNA data of 36 patients with ICC were downloaded from the TCGA database and divided into the high expression group and the low expression group according to the median of the overall FoxM1 expression value. The gene set enrichment analysis (GSEA) software was used for biological analysis. Informatics analysis to find possible differentially expressed genes between the high and low expressions of FoxM1 and related signal pathways that affect them. Real-time PCR (RT-PCR) was used to verify and compare the expression relationship of FoxM1 and P53 mRNA in ICC cell lines. Results GSEA analysis showed that there were significant differences in the expression of common gene signaling pathways such as P53 and MYC signaling pathways in the high FoxM1 expression group, while there were significant differences in the expression of FOXO signaling pathways in the low FoxM1 expression group (all FDR-Q values < 0.250). Rt-PCR results showed that the expression of P53 mRNA in HCC-9810-FOXM1 cells up-regulated by lentivirus transfection was significantly higher than that in control cells. The mRNA level of P53 in SSP-25-shFOXM1 cells down-regulated by FoxM1 was significantly lower than that in control cells (P < 0.000 1). Conclusion FoxM1 may play a broad role in the development of ICC and other different stages of evolution. Expression of FoxM1 may be related to P53, and FoxM1 in ICC may affect the P53 signaling pathway.

Key words： FoxM1 protein Intrahepatic cholangiocarcinoma Cell proliferation Signal pathways Computational biology Tumor suppressor protein P53

基金资助:广西壮族自治区科技基地和人才专项（桂科AD19110005）。

作者简介: 刘凌云（1982.6-），男，博士，副主任医师，桂林医学院附属医院肝胆胰外科实验室副主任；研究方向：肝癌基础及临床。毛涵（1996.12-），男，桂林医学院2020级肝胆外科专业在读硕士研究生；研究方向：肝胆胰肿瘤。 *具有同等贡献

引用本文:

刘凌云* 毛涵* 黄培露陈书乐. 基于GSEA分析FoxM1表达变化对人肝内胆管细胞癌增殖及侵袭相关信号通路的影响[J]. 中国医药导报, 2022, 19(29): 21-24,33.
LIU Lingyun* MAO Han* HUANG Peilu CHEN Shule . Analysis of the effect of FoxM1 expression on the proliferation and invasion related signaling pathways in intrahepatic cholangiocarcinoma based on GSEA. 中国医药导报, 2022, 19(29): 21-24,33.

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