MGAT4A在肺腺癌组织中的表达及其临床意义

Expression and clinical significance of MGAT4A in lung adenocarcinoma tissues

目的:探究α-1,3-甘露糖基糖蛋白4-β-N-乙酰氨基葡萄糖氨基转移酶A(MGAT4A)在肺腺癌(LUAD)组织中的表达情况,分析其在LUAD的发生、进展和预后的意义。方法:通过检索GEO等公共数据库,获得基因芯片数据集,选择样本数最大的GSE31210进行MGAT4A mRNA表达的计算;使用TCGA结合GTEx RNA测序数据集,进行第一轮验证;挑选基因芯片数据集中、样本数量排名第二的GSE40791,进行第二轮验证;收集3对广西医科大学第一附属医院的LUAD组织行RNA测序,进行第三轮验证;通过计算标准化均数差(SMD)及绘制综合受试者工作特征曲线(SROC),整合性分析了MGAT4A mRNA在上述4个LUAD数据集中的表达情况,进行第四轮验证。MGAT4A蛋白表达水平通过THPALUAD组织芯片使用免疫组化展示。通过绘制Kaplan-Meier生存曲线,研究MGAT4A在LUAD预后判断上的价值。通过对MGAT4A的相关基因进行功能富集分析,以探究其在LUAD发生发展中的潜在分子机制。结果:MGAT4A mRNA在4个数据集中均呈现出在LUAD组织中的低表达趋势(P<0.05)。整合858例LUAD组织分析,发现MGAT4A mRNA的SMD=-0.28, 95%CI=-0.42~-0.15。MGAT4A蛋白在LUAD中,亦有表达下降的趋势。MGAT4A的过表达,为LUAD预后的保护因素(P<0.05)。MGAT4A的负相关基因主要集中在"核糖体"、"新冠肺炎"、"过氧化物酶体"等通路上。结论:MGAT4A的表达下调或缺失,在LUAD的发生、进展及不良预后中发挥潜在的促进作用。

Objective: To investigate the expression, prognostic value, and pathogenesis of alpha-1,3-mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase A(MGAT4 A)in lung adenocarcinoma(LUAD)tissues.Methods: Public databases including GEO was searched to obtain relevant gene chip datasets. GSE31210 with the largest number of cases was selected to calculate MGAT4 A mRNA expression. TCGA combined with GTEx RNA-sequencing data was used for the first round of verification. The gene chip GSE40791, with the second most cases for LUAD, was chosen for the second round of verification. RNA-sequencing was carried out on 3 pairs of LUAD tissues collected in house for the third round of validation. The expression of MGAT4 A mRNA in the above four high throughput datasets was analyzed by calculating the standardized mean difference(SMD)and plotting the summarized receiver’s operating characteristic(SROC)curves comprehensively, for the fourth round of verification. The expression level of MGAT4 A protein was displayed by THPA tissue chip using immunohistochemistry. Kaplan-Meier curves was drawn, in order to study the prognostic value of MGAT4 A in LUAD.Lastly, through functional enrichment analysis on the basis of MGAT4 A-related genes, the potential molecular mechanism in the occurrence and development of LUAD was further explored.Results:MGAT4 A mRNA showed a markedly lower expression trend in LUAD tissues in the four datasets as compared to their controls. By integrating 858 LUAD cases, the SMD of MGAT4 A mRNA was-0.28(95% CI:-0.42,-0.15). MGAT4 A protein had a downward expression mode in LUAD as well.The overexpression of MGAT4 A was a protective factor for the prognosis of patients with LUAD. The negatively related genes of MGAT4 A were mainly enriched in the pathways of"ribosome","coronavirus disease-COVID-19", and"peroxisome". Conclusion: The down-regulation or absence of MGAT4 A, plays a potentially accelerating role in the occurrence, malignant progression, and deteriorated prognosis of patients with LUAD.