叶酸代谢通路基因在肝癌中的表达及意义

肝脏 ›› 2021, Vol. 26 ›› Issue (8): 851-856.

叶酸代谢通路基因在肝癌中的表达及意义

孙文文, 张凌云

200040 上海市第一妇婴保健院(孙文文);复旦大学附属中山医院(张凌云)

收稿日期:2021-03-19 出版日期:2021-08-31 发布日期:2021-09-29
通讯作者: 张凌云,Email: zhanglingyunyiya@163.com
基金资助:
国家自然科学基金(81902624)

Expression and significance of folate metabolic pathway genes in hepatocellular carcinoma——A bioinformatics analysis

SUN Wen-wen¹, ZHANG Ling-yun²

1. Shanghai First Maternity and Infant Hospital, Department of Pathology,Shanghai 200040, China;
2. Zhongshan Hospital of Fudan University, Department of Medical Oncology, Shanghai 200032, China

Received:2021-03-19 Online:2021-08-31 Published:2021-09-29
Contact: ZHANG Ling-yun, Email: zhanglingyunyiya@163.com

摘要/Abstract

摘要： 目的通过生物信息学分析叶酸代谢关键基因在肝癌中的表达、预后价值及与免疫微环境的相关性。方法利用Oncomine、GEPIA分析叶酸代谢关键基因在肝癌中的表达,采用cBioPortal分析肝癌患者中叶酸代谢关键基因的改变情况,Kaplan-Meier生存曲线分析与肝癌患者预后的关系,采用STRING、GeneMANIA构建叶酸代谢关键基因的互作网络,并通过TIMER数据库分析这些基因与免疫浸润细胞的相关性。结果通过Oncomine、GEPIA数据库发现在肝癌组织中MTR和MTHFD2的mRNA表达量分别是正常组织的2倍和1.6倍(P<0.05)。cBioPortal分析显示肝癌中叶酸代谢关键基因的改变,主要包括基因扩增、缺失突变和错义突变。Kaplan-Meier生存分析显示,MTHFR的高表达与肝癌患者预后差相关(HR=1.49,P=0.04);MTHFD1和SHMT1的高表达与肝癌患者预后良好相关(HR=0.63,P=0.0089和HR=0.52,,P=0.000 31)。TIMER数据库分析显示MTHFR和MTHFD2与B细胞、CD8⁺T淋巴细胞、CD4⁺T淋巴细胞、中性粒细胞、巨噬细胞和树突状细胞的浸润均呈正相关。结论叶酸代谢通路关键基因与肝癌患者预后、免疫细胞浸润存在显著相关性,是潜在的肝癌预后和治疗的靶点。

关键词: 肝癌, 叶酸代谢通路, 预后, 免疫, 生物信息学

Abstract: Objective To explore the expression level, prognostic value and relationship with immune microenvironment of folate metabolic pathway key genes (FMGs) in hepatocellular carcinoma (HCC) through bioinformatics analysis.Methods The expression levels of FMGs (MTR, MTHFR, MTHFD1, MTHFD2, SHMT1 and SHMT2) in HCC were analyzed by Oncomine and GEPIA. The relationship between FMGs and clinical prognosis was assessed by Kaplan-Meier survival curve. The genetic changes of FMGs were observed by cBioPortal. The interaction network of FMGs was constructed by STRING and GeneMANIA. The relationship of FMGs and immune infiltratimh cells was analyzed by TIMER database.Results Oncomine and GEPIA online analysis showed that the relative mRNA expression levels of MTR and MTHFD2 in HCC were 2 and 1.6 folder higher than those in normal liver tissues (P<0.05). cBioPortal analysis revealed that genetic changes of FMGs in HCC included gene amplification, deletion mutation and missense mutation. Kaplan-Meier survival analysis demonstrated that the high mRNA expression level of MTHFR was significantly associated with poor prognosis [hazard ratio (HR)=1.49, P=0.04], while the high expression levels of MTHFD1 and SHMT1 were significantly associated with favorable prognosis (HR=0.63, P=0.008 9 and HR=0.52, P=0.00031). TIMER analysis suggestted that MTHFR and MTHFD2 were postively correlated with the infiltration of diverse immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells.Conclusion FMGs is significantly correlated with the clinical prognosis of HCC patients and infiltration of immune cells, it is also a potential therapeutic target and a prognostic biomarker of HCC.

Key words: Hepatocellular carcinoma, Folate metabolic pathway, Prognosis, Immune, Bioinformatics

孙文文, 张凌云. 叶酸代谢通路基因在肝癌中的表达及意义[J]. 肝脏, 2021, 26(8): 851-856.

SUN Wen-wen, ZHANG Ling-yun. Expression and significance of folate metabolic pathway genes in hepatocellular carcinoma——A bioinformatics analysis[J]. Chinese Hepatolgy, 2021, 26(8): 851-856.

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