您的位置: 首页 > 2024年3月 第55卷 第3期 > 文字全文
2023年7月 第38卷 第7期11
目录

急性肺损伤相关分子标志物的鉴定及临床意义探索

Identification and clinical significance of molecular biomarkers associated with acute lung injury

来源期刊: 广州医药 | 245-254 发布时间:2024-04-12 收稿时间:2025/11/13 18:49:54 阅读量:16
作者:
关键词:
急性肺损伤GEO数据库关键基因蛋白互作网络分子标志物
acute lung injuryGEO databasekey geneprotein-protein interactionmolecular biomarker
DOI:
10.3969/j.issn.1000-8535.2024.03.005
收稿时间:
2023-08-30 
修订日期:
 
接收日期:
 
引用总数:
0  
目的 通过公共数据库筛选急性肺损伤(ALI)及急性呼吸窘迫综合征(ARDS)相关分子标志物,并探索其临床意义。方法 利用基因表达综合数据库(GEO)中有关ALI/ARDS基因表达芯片研究的两个数据集GSE76293和GSE10474,通过STRING网站和Cytoscape软件对差异基因进行蛋白互作网络分析并筛选ALI/ARDS相关关键基因。采用A549细胞构建ALI模型,并通过转录组测序验证关键基因在细胞中的表达差异情况。结果 2个GEO数据集中共筛选出共同上调基因27个,共同下调基因26个。主要参与抗原加工和外源抗原递呈、免疫受体活性调节、内质网膜构成等生物学功能,且与抗原加工、细胞分化等信号通路有关。蛋白互作网络分析共筛选出10个ALI/ARDS相关关键基因,分别为CD4、HLA-DQB1、CD74、HLA-DRA、FCGR2B、TOR1A、RELA、NME8、RNF19B、RHOB。细胞转录组测序结果显示,关键基因的上调或下调特征及表达差异情况与GEO数据集分析结果一致。结论 CD4等关键基因可能参与ALI/ARDS发生、发展的生物学过程,是ALI/ARDS临床诊断及预后预测的潜在个体化分子标志物。
Objective To identify molecular biomarkers associated with acute lung injury(ALI)/ acute respiratory distress syndrome(ARDS)and to explore their clinical significance with public databases. Methods Two datasets GSE76293 and GSE10474 in Gene Expression Omnibus(GEO)database for ALI/ARDS gene expression chip study were used to screen genes with significant differences in both datasets.The protein-protein interaction(PPI)analysis of co-expression genes was performed based on the STRING website and Cytoscape software,and then key genes related to ALI/ARDS were identified with cytoHubba method.The ALI model was constructed using A549 cells cultured in vitro,and the expression differences of key genes in the cells were verified by RNA sequencing. Results A total of 27 up-regulated genes and 26 down-regulated genes were screened in both the two GEO datasets with Venn Diagramm.These co-expression genes were mainly involved in biological functions such as antigen processing and presentation of exogenous peptide antigen,immune receptor activity,integral component of lumenal side of endoplasmic reticulum membrane and were related to signal pathways such as antigen processing and cell differentiation.A total of 10 key genes(CD4,HLA-DQB1,CD74,HLA-DRA,FCGR2B,TOR1A,RELA,NME8,RNF19B,RHOB)related to ALI/ARDS were identified. The results of cell RNA sequencing showed that the up-regulated or down-regulated characteristics and expression differences of key genes were consistent with the results of GEO datasets. Conclusions Several key genes identified in this study may be involved in the biological process of ALI/ARDS development,and may be potential individualized molecular markers for clinical diagnosis and prognosis prediction of ALI/ARDS.
1、 YANG J,PEI G,SUN X,et al.RhoB affects colitis through modulating cell signaling and intestinal microbiome[J].Microbiome,2022,10(1):149. YANG J,PEI G,SUN X,et al.RhoB affects colitis through modulating cell signaling and intestinal microbiome[J].Microbiome,2022,10(1):149.
2、 ZHANG D,LI B,GUO R,et al.RAB5C,SYNJ1,and RNF19B promote male ankylosing spondylitis by regulating immune cell infiltration[J].Ann Transl Med,2021,9(12):1011. ZHANG D,LI B,GUO R,et al.RAB5C,SYNJ1,and RNF19B promote male ankylosing spondylitis by regulating immune cell infiltration[J].Ann Transl Med,2021,9(12):1011.
3、 LIU Y,YU J T,WANG H F,et al.Association between NME8 locus polymorphism and cognitive decline,cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease[J].PLoS One,2014,9(12):e114777. LIU Y,YU J T,WANG H F,et al.Association between NME8 locus polymorphism and cognitive decline,cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease[J].PLoS One,2014,9(12):e114777.
4、 CHEN S,JIANG S,ZHENG W,et al.RelA/p65 inhibition prevents tendon adhesion by modulating inflammation,cell proliferation,and apoptosis[J].Cell Death Dis,2017,8(3):e2710. CHEN S,JIANG S,ZHENG W,et al.RelA/p65 inhibition prevents tendon adhesion by modulating inflammation,cell proliferation,and apoptosis[J].Cell Death Dis,2017,8(3):e2710.
5、 SAFFARI A,LAU T,TAJSHARGHI H,et al.The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders[J].Brain,2023,146(8):3273-3288. SAFFARI A,LAU T,TAJSHARGHI H,et al.The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders[J].Brain,2023,146(8):3273-3288.
6、 SAISORN W,SAITHONG S,PHUENGMAUNG P,et al.Acute kidney injury induced lupus exacerbation through the enhanced neutrophil extracellular traps(and apoptosis)in FCGR2B deficient lupus mice with renal ischemia reperfusion injury[J].Front Immunol,2021(12):669162. SAISORN W,SAITHONG S,PHUENGMAUNG P,et al.Acute kidney injury induced lupus exacerbation through the enhanced neutrophil extracellular traps(and apoptosis)in FCGR2B deficient lupus mice with renal ischemia reperfusion injury[J].Front Immunol,2021(12):669162.
7、 NOWICKA M,HILTON L K,ASHTON-KEY M,et al.Prognostic significance of FCGR2B expression for the response of DLBCL patients to rituximab or obinutuzumab treatment[J].Blood Adv,2021,5(15):2945-2957. NOWICKA M,HILTON L K,ASHTON-KEY M,et al.Prognostic significance of FCGR2B expression for the response of DLBCL patients to rituximab or obinutuzumab treatment[J].Blood Adv,2021,5(15):2945-2957.
8、 CHEN L,YIN Z,QIN X,et al.CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis[J].Pharmacol Res,2022(176):106086. CHEN L,YIN Z,QIN X,et al.CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis[J].Pharmacol Res,2022(176):106086.
9、 SU H,NA N,ZHANG X,et al.The biological function and significance of CD74 in immune diseases[J].Inflamm Res,2017,66(3):209-216. SU H,NA N,ZHANG X,et al.The biological function and significance of CD74 in immune diseases[J].Inflamm Res,2017,66(3):209-216.
10、 LIU D,HOFMAN P.Expression of NOTCH1,NOTCH4,HLA-DMA and HLA-DRA is synergistically associated with T cell exclusion,immune checkpoint blockade efficacy and recurrence risk in ER-negative breast cancer[J].Cell Oncol(Dordr),2022,45(3):463-477. LIU D,HOFMAN P.Expression of NOTCH1,NOTCH4,HLA-DMA and HLA-DRA is synergistically associated with T cell exclusion,immune checkpoint blockade efficacy and recurrence risk in ER-negative breast cancer[J].Cell Oncol(Dordr),2022,45(3):463-477.
11、 ZHAO Y,ZHAO Y,LI J,et al.HLA-DRB1*08:03:02 and HLA-DQB1*06:01:01 are associated with house dust mite-sensitive allergic rhinitis in Chinese subjects[J].Int Forum Allergy Rhinol,2016,6(8):854-861. ZHAO Y,ZHAO Y,LI J,et al.HLA-DRB1*08:03:02 and HLA-DQB1*06:01:01 are associated with house dust mite-sensitive allergic rhinitis in Chinese subjects[J].Int Forum Allergy Rhinol,2016,6(8):854-861.
12、 PAINTER M M,MATHEW D,GOEL R R,et al.Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination[J].Immunity,2021,54(9):2133-2142.e3. PAINTER M M,MATHEW D,GOEL R R,et al.Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination[J].Immunity,2021,54(9):2133-2142.e3.
13、 HU W,LIU D,LI R,et al.Comprehensive analysis of TRIM family genes in hepatitis virus B-related hepatoma carcinoma[J].Front Genet,2022(13):913743. HU W,LIU D,LI R,et al.Comprehensive analysis of TRIM family genes in hepatitis virus B-related hepatoma carcinoma[J].Front Genet,2022(13):913743.
14、 DESHAIES R J,JOAZEIRO C A P.RING domain E3 ubiquitin ligase[J].Annu Rev Biochem,2009(78):399-434. DESHAIES R J,JOAZEIRO C A P.RING domain E3 ubiquitin ligase[J].Annu Rev Biochem,2009(78):399-434.
15、 DONG J,GUO L,LIAO Z,et al.Increased expression of heat shock protein 70 in chronic obstructive pulmonary disease[J].Int Immunopharmacol,2013,17(3):885-893. DONG J,GUO L,LIAO Z,et al.Increased expression of heat shock protein 70 in chronic obstructive pulmonary disease[J].Int Immunopharmacol,2013,17(3):885-893.
16、 YOMBO D J K,MENTINK-KANE M M,WILSON M S,et al.Heat shock protein 70 is a positive regulator of airway inflammation and goblet cell hyperplasia in a mouse model of allergic airway inflammation[J].J Biol Chem,2019,294(41):15082-15094. YOMBO D J K,MENTINK-KANE M M,WILSON M S,et al.Heat shock protein 70 is a positive regulator of airway inflammation and goblet cell hyperplasia in a mouse model of allergic airway inflammation[J].J Biol Chem,2019,294(41):15082-15094.
17、 BELLANI G,LAFFEY J G,PHAM T,et al.Epidemiology,patterns of care,and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries[J].JAMA,2016,315(8):788-800. BELLANI G,LAFFEY J G,PHAM T,et al.Epidemiology,patterns of care,and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries[J].JAMA,2016,315(8):788-800.
18、 GIBSON P G,QIN L,PUAH S H.COVID-19 acute respiratory distress syndrome(ARDS):Clinical features and differences from typical pre-COVID-19 ARDS[J].Med J Aust,2020,213(2):54-56. GIBSON P G,QIN L,PUAH S H.COVID-19 acute respiratory distress syndrome(ARDS):Clinical features and differences from typical pre-COVID-19 ARDS[J].Med J Aust,2020,213(2):54-56.
19、 MURAKAMI N,HAYDEN R,HILLS T,et al.Therapeutic advances in COVID-19[J].Nat Rev Nephrol,2023,19(1):38-52. MURAKAMI N,HAYDEN R,HILLS T,et al.Therapeutic advances in COVID-19[J].Nat Rev Nephrol,2023,19(1):38-52.
20、 中华医学会重症医学分会.急性肺损伤/急性呼吸窘迫综合征诊断与治疗指南(2006)[J].中华内科杂志,2007,46(5):430-435. 中华医学会重症医学分会.急性肺损伤/急性呼吸窘迫综合征诊断与治疗指南(2006)[J].中华内科杂志,2007,46(5):430-435.
21、 LONG M E,MALLAMPALLI R K,HOROWITZ J C.Pathogenesis of pneumonia and acute lung injury[J].Clin Sci,2022,136(10):747-769. LONG M E,MALLAMPALLI R K,HOROWITZ J C.Pathogenesis of pneumonia and acute lung injury[J].Clin Sci,2022,136(10):747-769.
22、 MOLONEY E D,EVANS T W.Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome[J].Eur Respir J,2003,21(4):720-727. MOLONEY E D,EVANS T W.Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome[J].Eur Respir J,2003,21(4):720-727.
23、 HUANG C,WANG Y,LI X,et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China[J].Lancet,2020,395(10223):497-506. HUANG C,WANG Y,LI X,et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China[J].Lancet,2020,395(10223):497-506.
24、 Coronaviridae Study Group of the International Committee on Taxonomy of Viruses.The species severe acute respiratory syndrome-related coronavirus:Classifying 2019-nCoV and naming it SARS-CoV-2[J].Nat Microbiol,2020,5(4):536-544. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses.The species severe acute respiratory syndrome-related coronavirus:Classifying 2019-nCoV and naming it SARS-CoV-2[J].Nat Microbiol,2020,5(4):536-544.
25、 MATTHAY M A,WARE L B,ZIMMERMAN G A.The acute respiratory distress syndrome[J].J Clin Invest,2012,122(8):2731-2740. MATTHAY M A,WARE L B,ZIMMERMAN G A.The acute respiratory distress syndrome[J].J Clin Invest,2012,122(8):2731-2740.
26、 MOWERY N T,HILLMAN TERZIAN W T,NELSON A C.Acute lung injury[J].Curr Probl Surg,2020,57(5):100777. MOWERY N T,HILLMAN TERZIAN W T,NELSON A C.Acute lung injury[J].Curr Probl Surg,2020,57(5):100777.
上一篇
下一篇
出版者信息








《广州医药》公众号
目录