丁酰胆碱酯酶在胃癌中的预后价值及其生物学功能分析
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1.右江民族医学院研究生院;2.巴彦淖尔市医院中心实验室;3.南京医科大学附属南京医院病理科

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国家自然科学基金项目(面上项目,重点项目,重大项目)


The prognostic value and biological functions of butyrylcholinesterase in gastric cancer
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1.Graduate School of Youjiang Medical University for Nationalities;2.Department of Pathology,Nanjing First Hospital,Nanjing Medical University

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    摘要:

    目的:探究丁酰胆碱酯酶(bcylcholinesterase, BCHE)在胃癌(gastric cancer, GC)中的预后价值,验证和分析BCHE对胃癌细胞生物学功能的影响。研究方法:首先采用Lasso回归方法筛选预后基因,并利用卡方检验验证BCHE表达水平与临床病理参数之间的关系;其次利用TIMER2.0数据库和CIBERSORT算法研究BCHE和免疫细胞浸润之间相关性,WGCNA算法和DAVID Bioinformatics Resources数据库进行富集分析;最后利用qRT-PCR检测正常人胃上皮细胞系(GES-1)及人胃癌细胞系(HGC27和MKN1)中BCHE的表达情况;在HGC27和MKN1细胞系中瞬时转染小干扰RNA敲减BCHE后,利用CCK?8和克隆形成实验检测细胞增殖能力,黏附实验检测细胞黏附能力,Transwell和划痕实验检测细胞迁移、侵袭能力等功能变化情况。结果:利用Lasso回归分析筛选出15个与GC患者预后相关的基因,其中BCHE具有最佳的预测价值;进一步分析表明,BCHE在胃癌组织中的表达水平显著高于其在癌旁组织中的表达水平,且BCHE在肿瘤细胞中的表达与免疫细胞浸润密切相关。富集分析结果显示,BCHE高表达与细胞增殖、细胞迁移和细胞黏附等有关。体外实验进一步证实,降低BCHE的表达显著抑制胃癌细胞系的恶性生物学功能。结论:BCHE可作为GC的预后生物标志物,且可促进肿瘤内免疫细胞浸润;此外,降低BCHE表达可抑制其介导的恶性生物学功能。

    Abstract:

    Objective: Exploring the prognostic value of butyrylcholinesterase (BCHE) in gastric cancer (GC) and analyzing its impact on the biological functions of gastric cancer cells. Research methods: Firstly, Lasso regression method was used to screen prognostic genes, and the relationship between BCHE expression levels and clinical pathological parameters was verified using chi-square test. In addition, TIMER 2.0 database and CIBERSORT algorithm were utilized to investigate the correlation between BCHE and immune cell infiltration, and enrichment analysis was performed using WGCNA algorithm and DAVID Bioinformatics Resources database. Finally, the expression levels of BCHE in normal gastric epithelial cell line (GES-1) and gastric cancer cell lines (HGC27 and MKN1) were detected by real?time qPCR. Following transient transfection of small interfering RNA was conducted to knockdown the expression of BCHE in HGC27 and MKN1 cell lines. Cell proliferation was detected by CCK-8 and colony formation assay. Cell adhesion ability was detected by adhesion assay. Cell migration and invasion were detected by transwell and scratch assay. Results: Fifteen genes related to the prognosis of GC patients were screened using LASSO regression analysis. Among them, BCHE has the best predictive value. Further analysis indicated that the expression level of BCHE in GC tissues were higher than that in the adjacent tissues or healthy controls, while the expression of BCHE in tumor cells was closely related to immune cell infiltration related molecules. Enrichment analysis showed that the high expression of BCHE was related to cell proliferation, migration and adhesion. The results of in vitro experiments further confirmed that reducing the expression of BCHE significantly inhibited the malignant biological function of gastric cancer cell line. Conclusions: BCHE serve as a prognostic biomarker for GC and can promote immune cell infiltration in tumors. In addition, reducing the expression of BCHE can inhibit its mediated malignant biological function.

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  • 收稿日期:2023-06-10
  • 最后修改日期:2023-09-18
  • 录用日期:2023-10-18
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