doi:10.16597/j.cnki.issn.1002-154x.2022.02.002
基于 TCGA 数据库和蛋白 - 蛋白对接分析 DMGDH 在肾透明细胞癌组织中的表达及临床意义
韩君1∗ 张泽鑫2
(1.北京康仁堂药业有限公司,北京 101301; 2.广州中医药大学第一临床医学院,广东 广州 510405)
Analysis of DMGDH Expression in Tissues of Kidney Renal Clear Cell Carcinoma Based on TCGA Database and Protein-Protein Docking and Clinical Significance
Han Jun1∗; Zhang Zexin2;
(1. Beijing Tcmages Pharmaceutical Co. , Ltd. ,Beijing 101301;2. The First Clinical School of Guangzhou University of Chinese Medicine,Guangdong Guangzhou 510405)
摘要:
目的:本研究旨在明确二甲基甘氨酸脱氢酶(DMGDH)基因在泛癌中的表达情况及与患者预后的相关性,并 探讨 DMGDH 在肾透明细胞癌(KIRC) 中的相关功能及可能机制。 方法:利用癌症基因组图谱( TCGA) 数据分析 DMGDH 在泛癌中的表达差异情况,并通过 Cox 回归法分析 DMGDH 与各种肿瘤临床预后的相关性。 根据 DMGDH 的表达量,对差异表达的基因进行了基因功能注释(GO) 和基因组京都百科全书(KEGG) 功能富集分析。 最后使用 DMGDH 对过氧化物酶体增殖物激活受体( PPAR) 信号通路中的关键靶点蛋白过氧化物酶体增殖物激活受体 γ (PPARγ)、过氧化物酶体增殖物激活受体 α (PPARα)以及具有晶型结构细胞色素 P450(CYP450)亚型的受体蛋白细 胞色素 P450 家族 1 亚家族 B 成员 1(CYP1B1)进行蛋白 - 蛋白对接分析。 结果:TCGA 数据分析显示,DMGDH 在多 种肿瘤组织中显著下调,特别是 KIRC。 生存分析结果显示 DMGDH 在 KIRC 中是预后的保护因素,P 值为 3. 92e-07。 生存列线图结果显示 DMGDH、年龄和肿瘤(T)淋巴结(N)远处转移(M)分期是独立的预后因素,其生存模型 C 指数 (C - Index)为 0.776。 基因富集与功能分析显示 DMGDH 可能与羧酸转运和 PPAR 信号通路及细胞色素 P450 代谢有 关。 蛋白 - 蛋白对接结果 DMGDH 与 PPARγ、 PPARα 和 CYP1B1 蛋白结合较好。 结论:DMGDH 参与 KIRC 的发生和发展可能与 PPAR 信号通路和细胞色素 P450 代谢有关,DMGDH 可以作为 KIRC 预后的分子标志物。
关键词：DMGDH；肾透明细胞癌；预后；蛋白 - 蛋白对接；生物信息学；
Abstract：
Objective: This study is to disclose the correlation between expressions of DMGDH in generic cancers and prognosis of patients and discuss relevant functions and possible mechanism of DMGDH in Kidney renal clear cell carcinoma (KIRC). Methods: Expression differences of DMGDH in generic cancers were analyzed by The Cancer Genome Atlas (TCGA) and correlation between DMGDH and clinical prognosis of various tumors was analyzed by Cox regression. According to expression level of DMGDH, gene ontology ( GO) and kyoto encyclopedia of genes andgenomes (KEGG) functional enrichment analysis was performed to differentially expressed genes (DEGs). Finally, protein-protein docking analyses of key target proteins in peroxisome proliferators-activated receptors ( PPAR) signaling pathway, such as peroxisome proliferators-activated receptor γ (PPARγ), peroxisome proliferators-activated receptor α (PPARα) and Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) were carried out by using DMGDH. Results: TCGA data analysis showed that expression of DMGDH downregulated significantly in several tumor tissues, especially in KIRC. According to the survival analysis results, DMGDH was a protective factor of prognosis in KIRC, with a P value of 3. 92e - 07 . According to the survival nomogram, DMGDH, age and tumor (T) lymph node (N) distant metastasis (M) staging were independent prognosis factors and the C-index of the survival model was 0. 776. The gene enrichment and functional analysis showed that DMGDH might be related with carboxylic acid transportation, PPAR signal pathway and P450 metabolism. The protein-protein docking analysis results demonstrated that DMGDH could bind well with PPARγ, PPARα and CYP1B1. Conclusions: The participation of DMGDH in the genesis and development of KIRC might be related with PPAR signal pathway and P450 metabolism. DMGDH can be used as a molecular marker of prognosis of KIRC.
Keywords：DMGDH; clear cell renal carcinoma; prognosis; protein-protein docking; bioinformatics;