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鉴定出NUF2作为候选癌基因的综合多组学分析与非小细胞肺癌的不良预后和免疫浸润相关

Integrative Multi-Omics Analysis of Identified NUF2 as a Candidate Oncogene Correlates With Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer.

作者信息

Chen Mengqing, Li Shangkun, Liang Yuling, Zhang Yue, Luo Dan, Wang Wenjun

机构信息

Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Oncol. 2021 Jun 10;11:656509. doi: 10.3389/fonc.2021.656509. eCollection 2021.

DOI:10.3389/fonc.2021.656509
PMID:34178642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8222979/
Abstract

BACKGROUND

Lung cancer is one of the most common malignant tumors and the leading causes of cancer-related deaths worldwide. As a component of the nuclear division cycle 80 complex, NUF2 is a part of the conserved protein complex related to the centromere. Although the high expression of NUF2 has been reported in many different types of human cancers, the multi-omics analysis in non-small cell lung cancer (NSCLC) of NUF2 remains to be elucidated.

METHODS

In this analysis, NUF2 expression difference analysis in non-small cell lung cancer was evaluated by Oncomine, TIMER, GEO, and TCGA database. And the prognosis analysis of NUF2 based on Kaplan-Meier was performed. R language was used to analyze the differential expression genes, functional annotation and protein-protein interaction (PPI). GSEA analysis of differential expression genes was also carried out. Mechanism analysis about exploring the characteristic of NUF2, multi-omics, and correlation analysis was carried out using UALCAN, cBioportal, GEPIA, TIMER, and TISIDB, respectively.

RESULTS

The expression of NUF2 in NSCLC, both lung adenocarcinoma (LUAD) and squamous lung cancer (LUSC), was significantly higher than that in normal tissues. The analysis of UALCAN database samples proved that NUF2 expression was connected with stage and smoking habits. Meanwhile, the overall survival curve also validated that high expression of NUF2 has a poorer prognosis in NSCLC. GO, KEGG, GSEA, subcellular location from COMPARTMENTS indicated that NUF2 may regulate the cell cycle. Correlation analysis also showed that NUF2 was mainly positively associated with cell cycle and tumor-related genes. NUF2 altered group had a poorer prognosis than unaltered group in NSCLC. Immune infiltration analysis showed that the NUF2 expression mainly have negatively correlation with immune cells and immune subtypes in LUAD and LUSC. Furthermore, quantitative PCR was used to validate the expression difference of NUF2 in LUAD and LUSC.

CONCLUSION

Our findings elucidated that NUF2 may play an important role in cell cycle, and significantly associated with tumor-related gene in NSCLC; we consider that NUF2 may be a prognostic biomarkers in NSCLC.

摘要

背景

肺癌是全球最常见的恶性肿瘤之一,也是癌症相关死亡的主要原因。作为核分裂周期80复合体的一个组成部分,NUF2是一种与着丝粒相关的保守蛋白复合体的一部分。尽管已有报道称NUF2在许多不同类型的人类癌症中高表达,但NUF2在非小细胞肺癌(NSCLC)中的多组学分析仍有待阐明。

方法

在本分析中,通过Oncomine、TIMER、GEO和TCGA数据库评估非小细胞肺癌中NUF2的表达差异分析。并基于Kaplan-Meier法对NUF2进行预后分析。使用R语言分析差异表达基因、功能注释和蛋白质-蛋白质相互作用(PPI)。还对差异表达基因进行了基因集富集分析(GSEA)。分别使用UALCAN、cBioportal、GEPIA、TIMER和TISIDB对探索NUF2特征、多组学及相关性分析进行机制分析。

结果

NUF2在NSCLC(包括肺腺癌(LUAD)和肺鳞癌(LUSC))中的表达明显高于正常组织。对UALCAN数据库样本的分析证明,NUF2表达与分期和吸烟习惯有关。同时,总生存曲线也证实,在NSCLC中NUF2高表达预后较差。基因本体论(GO)、京都基因与基因组百科全书(KEGG)、GSEA、来自COMPARTMENTS的亚细胞定位表明,NUF2可能调控细胞周期。相关性分析还表明,NUF2主要与细胞周期和肿瘤相关基因呈正相关。在NSCLC中,NUF2改变组的预后比未改变组差。免疫浸润分析表明,在LUAD和LUSC中,NUF2表达主要与免疫细胞和免疫亚型呈负相关。此外,使用定量PCR验证了NUF2在LUAD和LUSC中的表达差异。

结论

我们的研究结果表明,NUF2可能在细胞周期中起重要作用,并且在NSCLC中与肿瘤相关基因显著相关;我们认为NUF2可能是NSCLC中的一种预后生物标志物。

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