付佳音,莫非,何芸,袁蕴馨,卢涵,渠巍,于湧
FU Jiayin,MO Fei,HE Yun,YUAN Yunxin,LU Han,QU Wei,YU Yong

• 1:贵州医科大学附属医院临床检验中心
• 2:贵州医科大学医学检验学院
• 3:贵州医科大学
• 4:贵阳市妇幼保健院检验科

摘要(Abstract)：

目的 探讨胃癌(GC)组织中碳酸酐酶(CAⅨ)的临床意义及其分子机制。方法 采用基因表达谱动态数据分析(GEPIA2)数据库预测GC组织中CAⅨ基因的差异性表达，利用癌症数据分析(UALCAN)数据库分析CAⅨ表达与GC患者临床病理特征的关系，采用Kaplan-Meier Plotter分析CAⅨ对GC的预后价值；收集10例GC患者的癌患组织(GC组)及其癌旁组织标本(对照组),采用免疫组织化学法检测CAⅨ表达；采用交互式基因检索工具(STRING)和可视代综合发现(DAVID)数据库进行基因本体论(GO)及京都基因与基因组百科全书(KEGG)通路分析预测CAⅨ的蛋白质互作关系及调控网络。结果 GEPIA2数据库结果显示，与对照组比较，GC组CAⅨ的表达量降低(P<0.05);UALCAN数据库显示，CAⅨ的表达与种族、肿瘤分化等级、幽门螺杆菌感染有相关性(P<0.05);Kaplan-Meier Plotter数据库分析显示，低CAⅨ表达组与高CAⅨ表达组的5年无进展生存期(PFS)相比，差异有统计学意义(P<0.05);临床标本免疫组织化学结果显示，GC组标本中CAⅨ表达量较对照组降低(P<0.05),与数据库预测结果一致；STRING数据库分析显示，CAⅨ与缺氧诱导因子-1α(HIF1α)、溶质载体家族4成员4(SLC4A4)、芳烃受体核转位器(ARNT)等蛋白具有较强相互作用关系；GO分析显示，CAⅨ参与低氧反应下RNA聚合酶Ⅱ启动子的转录调节等过程；KEGG分析显示CAⅨ与癌症信号通路、缺氧诱导因子-1(HIF-1)信号通路的调节有关。结论 CAⅨ在GC组织中呈低表达，其水平与GC患者肿瘤分化等级、PFS呈负相关，CAⅨ可能参与肿瘤代谢过程。
Objective To investigate clinical significance and molecular mechanism of carbonic anhydrase(CA Ⅸ) in gastric cancer(GC) tissues based on data mining analysis. Methods The GEPIA2 database was used to predict the differential expression of CA Ⅸ gene in GC tissues, the UALCAN database was used to analyze the relationship between CA Ⅸ expression and the clinicopathological characteristics of GC patients, and the Kaplan-Meier Plotter was used to analyze the prognostic value of CA Ⅸ on GC; cancerous tissues from 10 GC patients(GC group) and their paracancerous tissue specimens(the expression of CA Ⅸ was detected by immunohistochemistry in GC group and their paraneoplastic tissues(as the control group); the gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were performed by STRING and DAVID databases to predict the protein interactions and regulatory networks of CA Ⅸ. Results GEPIA2 database showed that the expression of CA Ⅸ was reduced in GC group compared with the control group(P<0.05). The UALCAN database showed that the expression of CA Ⅸ was correlated with race, tumour differentiation grade and H. pylori infection(P<0.05); The Kaplan-Meier Plotter database analysis showed a statistically significant difference in 5-year progression-free survival(PFS) between the low CA Ⅸ-expressing group and the high CA Ⅸ-expressing group(P<0.05). The immunohistochemical results of clinical specimens showed that CA Ⅸ expression was significantly lower in the cancerous tissues of GC group compared with the paracancerous tissues of the control group(P<0.05), which was consistent with the predicted results of the database. The STRING database showed that CA Ⅸ had strong interactions with hypoxia-inducible factor-1a(HIF1A), solute carrier family 4 member 4(SLC4A4) and arylhydrocarbon receptor nuclear translocator(ARNT) proteins. The GO analysis of CA Ⅸ and interacting proteins showed involvement in processes such as transcriptional regulation of RNA polymerase Ⅱ promoter in response to hypoxia. KEGG analysis of CA Ⅸ showed it was associated with the cancer signalling pathway and the regulation of hypoxia-inducible factor-1(HIF-1) signalling pathway. Conclusion CA Ⅸ is lowly expressed in GC tissues, and its level is negatively correlated with tumour differentiation grade and PFS in GC patients, and can be involved in tumour metabolic pathways.

关键词(KeyWords)： 数据挖掘;胃肿瘤;碳酸酐酶Ⅸ;差异表达;基因本体分析;京都基因与基因组百科全书通路分析
data mining;stomach neoplasms;carbonic anhydrase Ⅸ(CAⅨ);differential expression;gene ontology(GO) analysis;Kyoto encyclopedia of gene and genomes(KEGG) pathway analysis

Abstract:

Keywords:

基金项目(Foundation): 贵州医科大学国家自然科学基金培育项目(gyfynsfc[2020]-1)

作者(Author): 付佳音,莫非,何芸,袁蕴馨,卢涵,渠巍,于湧
FU Jiayin,MO Fei,HE Yun,YUAN Yunxin,LU Han,QU Wei,YU Yong

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