NADH：泛醌氧化还原酶复合体组装因子2在肝癌组织中的异常表达和功能探讨

肝癌电子杂志 ›› 2022, Vol. 9 ›› Issue (1): 29-35.

NADH：泛醌氧化还原酶复合体组装因子2在肝癌组织中的异常表达和功能探讨

朱影, 谷兴璐, 赵晓航, 孙玉琳^*

国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室,北京 100021

收稿日期:2021-10-09 出版日期:2022-03-31 发布日期:2022-10-28
通讯作者: ^*孙玉琳,E-mail：ylsun@cicams.ac.cn
作者简介:朱影, 硕士研究生, 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学国家重点实验室
基金资助:
国家自然科学基金（82073327）

Clinical significance and functional analysis of NADH: ubiquinone oxidoreductase complex assembly factor 2 in liver cancer

Zhu Ying, Gu Xinglu, Zhao Xiaohang, Sun Yulin^*

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China

Received:2021-10-09 Online:2022-03-31 Published:2022-10-28

摘要/Abstract

摘要： 目的: 基于肿瘤基因组图谱（the cancer genome atlas,TCGA）数据库的多组学数据,分析线粒体呼吸链复合体I组装因子NADH∶泛醌氧化还原酶复合体组装因子2（NADH∶ubiquinone oxidoreductase complex assembly factor 2,NDUFAF2）基因在肝癌组织中的表达、临床及预后意义,并探讨其参与肝癌发生发展的可能机制。
方法: 利用TCGA肝癌样本的RNA测序、全外显子组测序、单核苷酸多态芯片和DNA甲基化测序数据,分析NDUFAF2在肝癌中的表达特征及其异常高表达的可能机制。基于TCGA肝癌RNA测序数据获得与NDUFAF2高度相关性的共表达基因,进行Reactome、MSigDB通路和人类表型富集分析,并利用Cytoscape软件绘制功能网络。
结果: 对TCGA肝癌RNA测序数据的表达和生存分析显示,线粒体呼吸链复合体的全部亚基中,仅NDUFAF2在肝癌组织中显著高表达,且与不良的总生存率和无复发生存率均相关。肝癌组织中NDUFAF2的高表达与性别、人种、肿瘤分化程度和微血管侵犯显著相关（P均<0.05）。基因扩增和肝癌驱动基因TP53和CTNNB1的突变,以及MYC扩增是造成NDUFAF2高表达的可能原因。对肝癌组织中与NDUFAF2共表达的411个基因的富集分析显示,NDUFAF2可能通过调控细胞能量产生、氧化应激、RNA加工、蛋白翻译和c-Myc、mTORC1相关信号传导通路,促进肝癌的发生发展。
结论: NDUFAF2在肝癌组织中的高表达可能通过调控RNA加工和蛋白翻译等生物学通路参与细胞癌变,可作为潜在的肝癌预后预测标志物和新的治疗干预靶点。

关键词: NADH：泛醌氧化还原酶复合体组装因子2, 肝癌, 公共数据挖掘, 预后, 表达调控, 肿瘤发生发展

Abstract: Objective:To investigate the expression characteristics, clinical and prognostic significance as well as potential functional mechanisms of NADH: ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2) in liver cancer based on multi-omics data from The Cancer Genome Atlas (TCGA) database.
Method:RNA sequencing, whole exome sequencing, single nucleotide polymorphism microarray and DNA methylation sequencing data of TCGA liver cancer samples were used to analyze the expression characteristics and possible causes for abnormally high expression of NDUFAF2 in liver. The highly correlated co-expressed genes with NDUFAF2 were used to perform the pathways and human phenotype enrichment analyses, and then the functional network was constructed using Cytoscape software.
Result:Expression and survival analysis based on RNA sequencing data from liver cancer patients of TCGA showed that among all subunits of the mitochondrial respiratory complexes, only NDUFAF2 was significantly overexpressed in tumor tissues and correlated with unfavorable overall survival and recurrence-free survival. Elevated expression of NDUFAF2 was associated with gender, race, tumor differentiation and microvascular invasion (all P<0.05). Copy number gain, TP53 and CTNNB1 missense mutation as well as MYC amplification but not promoter methylation were all responsible for high NDUFAF2 expression in tumor. The enrichment analysis of 411 genes that co-expressed with NDUFAF2 revealed that NDUFAF2 may contribute to hepatocarcinogenesis by regulating cellular energy production, oxidative stress, RNA processing, protein translation and c-Myc and mTORC1-related pathways.
Conclusion:Elevated expression of NDUFAF2 in liver cancer maybe engage in carcinogenesis by facilitating RNA processing, protein translation and intracellular signaling pathways. NDUFAF2 can serve as a potential prognostic marker and a new target for therapeutic intervention for liver cancer.

Key words: NADH: ubiquinone oxidoreductase complex assembly factor 2, Liver cancer, Public database mining, Prognosis, Expression regulation, Tumorigenesis

朱影, 谷兴璐, 赵晓航, 孙玉琳. NADH：泛醌氧化还原酶复合体组装因子2在肝癌组织中的异常表达和功能探讨[J]. 肝癌电子杂志, 2022, 9(1): 29-35.

Zhu Ying, Gu Xinglu, Zhao Xiaohang, Sun Yulin. Clinical significance and functional analysis of NADH: ubiquinone oxidoreductase complex assembly factor 2 in liver cancer[J]. Electronic Journal of Liver Tumor, 2022, 9(1): 29-35.

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