[1]王 云,肖 宁,段欢欢.基于GEO数据库筛选金黄色葡萄球菌脓毒症中差异表达的ceRNA及验证[J].现代检验医学杂志,2026,41(03):115-118+125.[doi:10.3969/j.issn.1671-7414.2026.03.021]
 WANG Yun,XIAO Ning,DUAN Huanhuan.Screening and Validation of Differentially Expressed ceRNA in Staphylococcus Aureus Sepsis Based on GEO Database[J].Journal of Modern Laboratory Medicine,2026,41(03):115-118+125.[doi:10.3969/j.issn.1671-7414.2026.03.021]
点击复制

基于GEO数据库筛选金黄色葡萄球菌脓毒症中差异表达的ceRNA及验证()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第41卷
期数:
2026年03期
页码:
115-118+125
栏目:
论著
出版日期:
2026-05-13

文章信息/Info

Title:
Screening and Validation of Differentially Expressed ceRNA in Staphylococcus Aureus Sepsis Based on GEO Database
文章编号:
1671-7414(2026)03-115-05
作者:
王 云肖 宁段欢欢
邯郸市中心医院,河北邯郸 056001
Author(s):
WANG YunXIAO NingDUAN Huanhuan
Handan Central Hospital,Hebei Handan 056001,China
关键词:
金黄色葡萄球菌脓毒症差异表达基因生物信息学分析竞争性内源RNA血流感染
分类号:
R378.11;Q786
DOI:
10.3969/j.issn.1671-7414.2026.03.021
文献标志码:
A
摘要:
目的?基于基因表达综合(GEO)数据库,筛选金黄色葡萄球菌脓毒症的差异表达基因(DGEs),并构建竞争性内源RNA(ceRNA)调控网络,以便深入了解金黄色葡萄球菌脓毒症发病机制。方法在GEO数据库中检索金黄色葡萄球菌血流感染(BSI)基因表达数据集,下载使用GSE33341数据集,筛选金黄色葡萄球菌脓毒症的DGEs,采用京都基因与基因组百科全书(KEGG)对DGEs进行富集分析。基于ceRNA的理论,构建长链非编码RNA(lnRNA)的调控网络。最后,收集2022年1月~2023年12月于邯郸市中心医院治疗的84例脓毒症患者为研究对象,根据是否为金黄色葡萄球菌感染分为金黄色葡萄球菌组(n=42)和对照组(n=42),提取样本RNA,采用实时荧光定量PCR(qRT-PCR)方法对筛选基因验证。结果获得81个lncRNA,114个miRNA,76个mRNA构建lncRNA-miRNA-mRNA的ceRNA调控网络,最终共获得3个金黄色葡萄球菌相关致病基因,具体为lncRNAX染色体失活特异转录因子(XIST)、核旁斑组装转录本1(NEAT1)和肺腺癌转移相关转录本1(MALAT1)。KEGG富集分析显示差异基因主要通过Th17细胞分化、Th1和Th2细胞分化、T细胞受体信号通路、鞘脂信号通路、逆行内源性大麻素信号、Ras信号通路、磷酸酰肌醇3激酶(PI3K)-蛋白激酶B(Akt)信号通路、氧化磷酸化、自然杀伤(NK)细胞介导的细胞毒性、丝裂原活化蛋白激酶(MAPK)信号通路、叉头框O(FoxO)信号通路、FcεRI信号通路、细胞凋亡生物过程参与金黄色葡萄球菌的感染。qRT-PCR对临床样本中关键基因表达检测显示,相对于对照组,金黄色葡萄球菌组血液中表达上调的基因有lncRNAXIST、lncRNANEAT1和lncRNAMALAT1,差异具有统计学意义(t=11.387、10.444、23.183,均P<0.001);实验结果与生物信息学分析结果一致。结论通过生物信息学筛选出金黄色葡萄球菌脓毒症关键基因lncRNAXIST、NEAT1和MALAT1,可能成为金黄色葡萄球菌脓毒症诊断和治疗的潜在靶点,为金黄色葡萄球菌脓毒症的临床诊疗提供新的思路。
Abstract:
Objective To screen differentially expressed genes (DGEs) in staphylococcus aureus sepsis and construct a competing endogenous RNA (ceRNA) regulatory network based on the Gene Expression Omnibus (GEO) database, in order to gain deeper insights into the pathogenesis of Staphylococcus aureus sepsis. Methods The gene expression data set of Staphylococcus aureus bloodstream infection (BSI) was retrieved from GEO database, and the differentially expressed genes of Staphylococcus aureus sepsis were screened using GSE33341 dataset. The enrichment analysis on DGEs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). The regulatory network of for long non-coding RNAs (lnRNAs) was constructed based on ceR-NA theory. Finally, 84 patients with sepsis treated in Handan Central Hospital from January 2022 to December 2023 were col-lected as research objects. Patients were divided into a Staphylococcus aureus group (n=42) and a control group (n=42) based on infection status. RNA was extracted from samples, and the selected genes were validated using quantitative real time polymerase chain reaction (qRT-PCR). Results 81 lncRNAs, 114 miRNAs and 76 mRNAs were obtained to construct the ceRNA regulatory network of lncRNA-miRNA-mRNA. Finally, a total of 3 pathogenic genes related to staphylococcus aureus were obtained, spe-cifically lncRNA XIST, NEAT1 and MALAT1. KEGG enrichment analysis showed that the DEGs primarily functioned through Th17 cell differentiation, Th1 and Th2 cell differentiation, T cell receptor signaling, sphingolipid signaling, retrograde endo-cannabinoid signaling, Ras signaling, PI3K-Akt signaling, oxidative phosphorylation, natural killer cell-mediated cytotoxicity, MAPK signaling, FoxO signaling, FCεRI signaling, apoptotic biological processes involved in staphylococcus aureus infection.RT-qPCR detection of key gene expression in clinical samples showed that compared with the control group, the Staphylococcus aureus group exhibited statistically significant upregulation of lncRNA XIST, lncRNA NEAT1, lncRNA MALAT1 in blood sam-ples, the differences were statistically significant (t=11.387, 10.444, 23.183, all P<0.001). The experimental results were consis-tent with bioinformatics analysis findings. Conclusions Bioinformatics screening identified lncRNA XIST, NEAT1 and MALAT1 as key genes in Staphylococcus aureus sepsis. These may serve as potential targets for diagnosis and treatment of Staphylococcus aureus sepsis, offering new insights for clinical management.

参考文献/References:

[1] PICKENS C I, WUNDERINK R G. Methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia/ventilator-associated pneumonia[J]. Seminars in Respira-tory and Critical Care Medicine, 2022, 43(2): 304-309.
[2] LIU D, HUANG S Y, SUN J H, et al. Sepsis-induced immu-nosuppression: mechanisms, diagnosis and current treatment options [J]. Military Medical Research , 2022, 9(1): 56.
[3] HEMMADI V, BISWAS M. An overview of moon-lighting proteins in Staphylococcus aureus infection[J]. Archives of Microbiology, 2021, 203(2): 481-498.
[4] KOHANSAL M, ALGHANIMI Y K, BANOON S R, et al. CircRNA-associated ceRNA regulatory networks as emerging mechanisms governing the development and biophysiopathology of epilepsy[J]. CNS Neuroscience& Therapeutics, 2024, 30(4): e14735.
[5] CHU S F, ZHAO T Q, LI M X, et al. Long non-coding RNA (CMR) involved in autoprotection in S. aureus mas-titis in dairy cows by regulating miR-877/FOXM1 [J]. Ec-otoxicology and Environment Safety, 2024, 278: 116456.
[6] KAMALI M J, SALEHI M, MOSTAFAVI M, et al. Hi-jacking and rewiring of host circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory net-works by oncoviruses during development of viral can-cers[J]. Reviews in Medical Virology, 2024, 34(2): e2530.
[7] ALBERT VEGA C, KARAKIKE E, BARTOLO F, et al. Differential response induced by LPS and MPLA in immunocompetent and septic individuals [J]. Clinical Immunology, 2021, 226: 108714.
[8] PEYRUSSON F, NGUYEN T K, NAJDOVSKI T, et al. Host cell oxidative stress induces dormant Staphylococcus aureus persisters [J]. Microbiology Spectrum, 2022, 10(1): e0231321.
[9] 杨斌,李华.2016~2019年陕西省榆林市细菌耐药监测网成员单位金黄色葡萄球菌的临床分布与耐药性变迁[J].现代检验医学杂志,2021,36(1):81-84. YANG B, LI H. Clinical distribution and drug resis-tance changes of Staphylococcus aureus , a member of the bacterial resistance monitoring network in Yulin, Shaanxi province from 2016 to 2019[J]. Journal of Modern Laboratory Medicine, 2021, 36(1): 81-84.
[10] LEE L N, CHOU W R, WANG J Y, et al. Characteris-tics and local risk factors of community-acquired and health-care-associated Staphylococcus aureus pneumo-nia[J]. Scientific Reports, 2022, 12(1): 18670.
[11] 冯华,薛洪刚,徐玉秀.难治性肺炎支原体肺炎患儿血清长链非编码RNA肺腺癌转移相关转录因子1和烟酰胺核苷酸反义转氢酶RNA1检测的临床意义[J].现代检验医学杂志,2022,37(4):7-12, 164. FENG H, XUE H G, XU Y X. Clinical significance of serumlong non-coding RNA metastasis-associated lung adenocarcinoma transcript 1, nicotinamide nucleotide transhydrogenase-antisense RNA1 in children with refrac-tory Mycoplasma pneumoniae pneumonia[J]. Journal of Modern Laboratory Medicine, 2022, 37(4): 7-12, 164.
[12] YU J L, LI M Z, WANG J, et al. Identification of Staph-ylococcus aureus virulence-modulating RNA from tran-scriptomics data with machine learning[J]. Virulence, 2023, 14(1): 2228657.
[13] 白文筠,梁峻尉,王晓燕.胃癌前病变和胃癌差异表达的 mRNA?circRNA调控网络及关键调控轴的鉴定[J].中国老年学杂志,2024,44(10):2327-2336. BAI W J, LIANG J W, WANG X Y. Identification of differentially expressed mRNA, circRNA regulatory network and key regulatory axes in precancerous le-sions and gastric cancer[J]. Chinese Journal of Geron-tology, 2024, 44(10): 2327-2336.
[14] WANG H F, LI Y C, JIANG S Q, et al. LncRNA xist reg-ulates sepsis associated neuroinflammation in the periven-tricular white matter of CLP rats by miR-122-5p/PKCη axis [J]. Frontiers in Immunology, , 2023, 14: 1225482.
[15] MA M R, PEI Y F, WANG X X, et al. LncRNA XIST mediates bovine mammary epithelial cell inflammatory response via NF-κB/NLRP3 inflammasome path-way[J]. Cell Proliferation, 2019, 52(1): e12525.
[16] CHEN Z Z, HU X, WU Y, et al. Long non-coding RNA XIST promotes the development of esophageal cancer by sponging miR-494 to regulate CDK6 expression [J]. Bio-medicine & Pharmacotherapy, 2019, 109: 2228-2236.
[17] LI X Y, YE S L, LU Y. Long non-coding RNA NEAT1 overexpression associates with increased exacerbation risk, severity, and inflammation, as well as decreased lung function through the interaction with microRNA-124 in asthma[J]. Journal of Clinical Laboratory Analysis, 2020, 34(1): e23023.
[18] NONG W X. Long non-coding RNA NEAT1/miR-193a-3p regulates LPS-induced apoptosis and inflam-matory injury in WI-38 cells through TLR4/NF-κB signaling[J]. American Journal of Translational Re-search, 2019, 11(9): 5944-5955.
[19] AHMAD I, NAQVI R A, VALVERDE A, et al. Ln-cRNA MALAT1/microRNA-30b axis regulates macro-phage polarization and function [J]. Frontiers in Immu-nology, 2023, 14: 1214810.
[20] GU X D, HOU J Y, RAO J W, et al. LncRNA MALAT1 suppresses monocyte-endothelial cell interactions by targeting miR-30b-5p and enhancing ATG5-mediated autophagy[J]. Heliyon, 2024, 10(7): e28882.

相似文献/References:

[1]聂署萍,张 扬,王 琼,等.红霉素体外诱导金黄色葡萄球菌耐药分析[J].现代检验医学杂志,2016,31(01):138.[doi:10.3969/j.issn.1671-7414.2016.01.040]
 NIE Shu-ping,ZHANG Yang,WANG Qiong,et al.Drug-Resistance of Staphylococcus Aureus Induced by Erythromycin in Vitro[J].Journal of Modern Laboratory Medicine,2016,31(03):138.[doi:10.3969/j.issn.1671-7414.2016.01.040]
[2]刘 青,樊 冰.儿童呼吸道感染患者金黄色葡萄球菌的分离与耐药性分析[J].现代检验医学杂志,2016,31(03):150.[doi:10.3969/j.issn.1671-7414.2016.03.042]
 LIU Qing,FAN Bing.Separation and Analysis of Drug Resistance of Staphylococcus Aureus in Patients with Respiratory Infection of Children[J].Journal of Modern Laboratory Medicine,2016,31(03):150.[doi:10.3969/j.issn.1671-7414.2016.03.042]
[3]谢娜,饶国洲,朱勇,等.单极射频低温等离子体杀菌的实验研究[J].现代检验医学杂志,2015,30(05):87.[doi:10.3969/j.issn.1671-7414.2015.05.026]
 XIE Na,RAO Guo-zhou,ZHU Yong,et al.Experimental Study on Monopole Radio Frequency Low Temperature Plasma Sterilization[J].Journal of Modern Laboratory Medicine,2015,30(03):87.[doi:10.3969/j.issn.1671-7414.2015.05.026]
[4]沈丽娟,孙 杰,吴 晓,等.老年脓毒症患者血清清蛋白水平与其危重程度及预后的相关性[J].现代检验医学杂志,2017,32(01):131.[doi:10.3969/j.issn.1671-7414.2017.01.036]
 SHEN Li-juan,SUN Jie,WU Xiao,et al.Relationship of Albumin Levels with the Prognosis and Severity of Illness among Elderly Sepsis Patients[J].Journal of Modern Laboratory Medicine,2017,32(03):131.[doi:10.3969/j.issn.1671-7414.2017.01.036]
[5]景双艳,王晓宁,魏莲花,等.金黄色葡萄球菌表面蛋白Ebh致病性的研究进展[J].现代检验医学杂志,2019,34(02):156.[doi:10.3969/j.issn.1671-7414.2019.02.040]
 JING Shuang-yan,WANG Xiao-ning,WEI Lian-hua,et al.Advances in Research on Pathogenicity ofStaphylococcus Aureus Surface Protein Ebh[J].Journal of Modern Laboratory Medicine,2019,34(03):156.[doi:10.3969/j.issn.1671-7414.2019.02.040]
[6]王 蓉,陈紫茹,唐露丹,等.广州市第一人民医院新生儿病区金黄色葡萄球菌毒力基因分布分析[J].现代检验医学杂志,2019,34(06):63.[doi:10.3969 / j.issn.1671-7414.2019.06.015]
 WANG Rong,CHEN Zi-ru,TANG Lu-dan,et al.Analysis of Virulence Gene Distribution of Staphylococcus Aureus in Neonatal Disease Area from the First People’s Hospital of Guangzhou[J].Journal of Modern Laboratory Medicine,2019,34(03):63.[doi:10.3969 / j.issn.1671-7414.2019.06.015]
[7]佟 丽,黄丽萍,石晓霞,等.血栓弹力图检测新型冠状病毒肺炎患者凝血功能的探讨分析[J].现代检验医学杂志,2020,35(04):97.[doi:10.3969/j.issn.1671-7414.2020.04.024]
 TONG Li,HUANG Li-ping,SHI Xiao-xia,et al.Investigation and Analysis of Thromboelastography in the Detection of COVID-19 Patients[J].Journal of Modern Laboratory Medicine,2020,35(03):97.[doi:10.3969/j.issn.1671-7414.2020.04.024]
[8]肖武强,徐敏丹,吴先正.脓毒症患者血清肠型脂肪酸结合蛋白、二胺氧化酶水平检测对早期肠组织损伤及预后的评估价值[J].现代检验医学杂志,2021,36(01):10.[doi:10.3969/j.issn.1671-7414.2021.01.003]
 XIAO Wu-qiang,XU Min-dan,WU Xian-zheng.Evaluation Value of Serum Intestinal Fatty Acid Binding Protein and Diamine Oxidase in the Early Stage of Intestinal Tissue Injury and Prognosis in Patients with Sepsis[J].Journal of Modern Laboratory Medicine,2021,36(03):10.[doi:10.3969/j.issn.1671-7414.2021.01.003]
[9]杨 斌,李 华.2016~2019年陕西省榆林市细菌耐药监测网成员单位金黄色葡萄球菌的临床分布与耐药性变迁[J].现代检验医学杂志,2021,36(01):81.[doi:10.3969/j.issn.1671-7414.2021.01.021]
 YANG Bin,LI Hua.Clinical Distribution and Drug Resistance Changes of Staphylococcus Aureus, A Member of the Bacterial Resistance Monitoring Network in Yulin, Shaanxi Province from 2016 to 2019[J].Journal of Modern Laboratory Medicine,2021,36(03):81.[doi:10.3969/j.issn.1671-7414.2021.01.021]
[10]张 晨,孙虹佳.新型感染标志物在脓毒症早期诊断中的应用及研究进展[J].现代检验医学杂志,2021,36(01):156.[doi:10.3969/j.issn.1671-7414.2021.01.038]
 ZHANG Chen,SUN Hong-jia.Latest Research Progress of Early Serum Inflammatory and Oxidative Stress Mediator of Sepsis[J].Journal of Modern Laboratory Medicine,2021,36(03):156.[doi:10.3969/j.issn.1671-7414.2021.01.038]

备注/Memo

备注/Memo:
基金项目:河北省中医药管理局科研计划项目(编号:2022660)。
作者简介:王云(1984-),女,本科,主管护师,研究方向:金黄色葡萄球菌脓毒症,E-mail:wy667712@126.com。
通讯作者:肖宁(1979-),女,硕士,副主任医师,主要研究方向:金黄色葡萄球菌脓毒症,E-mail:xiaoning2017@126.com。
更新日期/Last Update: 2026-05-15