[1]侯 丽,张 丽,唐 婧,等.基于GEO 对多发性骨髓瘤关键基因生物信息学分析及免疫浸润模式与验证[J].现代检验医学杂志,2023,38(05):23-28.[doi:10.3969/j.issn.1671-7414.2023.05.005]
 HOU Li,ZHANG Li,TANG Jing,et al.Bioinformatics Analysis and Verify Core Genes and Immune Infiltration Patterns in Multiple Myeloma Based on GEO[J].Journal of Modern Laboratory Medicine,2023,38(05):23-28.[doi:10.3969/j.issn.1671-7414.2023.05.005]
点击复制

基于GEO 对多发性骨髓瘤关键基因生物信息学分析及免疫浸润模式与验证()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年05期
页码:
23-28
栏目:
论著
出版日期:
2023-09-15

文章信息/Info

Title:
Bioinformatics Analysis and Verify Core Genes and Immune Infiltration Patterns in Multiple Myeloma Based on GEO
文章编号:
1671-7414(2023)05-023-06
作者:
侯 丽1张 丽1唐 婧1牛 瑶1张 媛2朱有森1
(1. 新疆医科大学第一附属医院医学检验中心,乌鲁木齐 830054;2. 喀什地区第二人民医院检验科,新疆喀什 844000)
Author(s):
HOU Li1 ZHANG Li1 TANG Jing1 NIU Yao1 ZHANG Yuan2 ZHU Yousen1
(1. Medical Laboratory Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; 2. Department of Clinical Laboratory, the Second People’s Hospital of Kashi Prefecture, Xinjiang Kashi 844000, China)
关键词:
生物信息学多发性骨髓瘤免疫浸润
分类号:
R733.3;Q786
DOI:
10.3969/j.issn.1671-7414.2023.05.005
文献标志码:
A
摘要:
目的 通过生物信息学方法筛选多发性骨髓瘤(multiple myeloma,MM)潜在的关键基因,并分析其免疫浸润模式。方法 从基因表达综合数据库(gene expression omnibus,GEO) 获取与多发性骨髓瘤相关的基因表达谱GSE118985,(GSE133346和GSE146649),采用生物信息学方法筛选与多发性骨髓瘤相关的差异表达基因(DEGs)并进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG) 富集分析、免疫细胞浸润分析。通过蛋白质- 蛋白质相互作用网络筛选出多发性骨髓瘤潜在的关键基因,利用数据GSE7116 验证关键基因在多发性骨髓瘤中的诊断价值并绘制受试者工作特征(receiver operator characteristic,ROC)曲线。结果 共筛选出101 个DEGs。GO 功能注释和KEGG 富集分析显示,DEGs 主要富集在免疫反应过程中,细胞因子受体相互作用、细胞外基质受体相互作用、粘着斑和Hedgehog 信号通路等,单核细胞是多发性骨髓瘤最主要的免疫浸润细胞。最终筛选出5 个关键基因,分别为SDC1,IRF4,CD38,TNFRSF17和CCND1,核心基因对验证模型联合诊断的AUC 为0.933。结论 SDC1,IRF4,CD38,TNFRSF17 和CCND1 在多发性骨髓瘤中均上调,联合诊断的效能较高,可能是多发性骨髓瘤潜在的生物标志物,可为以后治疗提供新的思路。
Abstract:
Objective To screen the potential key genes of multiple myeloma (MM) and analyze its immune infiltration pattern by bioinformatics methods. Methods The gene expression profiles (GSE118985,GSE133346 and GSE146649) related to multiple myeloma were obtained from Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) related to multiple myeloma were screened by bioinformatics methods. Gene ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and immune cell infiltration analysis were performed. The potential key genes of multiple myeloma were screened by protein-protein interaction network, and the data GSE7116 was used to verify the diagnostic value of key genes in multiple myeloma , and the ROC curve was drawn. Results A total of 101 DEGs were screened. GO functional annotation and KEGG enrichment analysis showed that DEGs were mainly enriched in the process of immune response, cytokine receptor interaction, extracellular matrix receptor interaction, focal adhesion, Hedgehog signaling pathway, etc. Monocytes are the most important immune infiltrating cells in multiple myeloma. Five key genes were selected, namely SDC1,IRF4,CD38,TNFRSF17 and CCND1. The AUC of the core genes for the combined diagnosis of the validation model was 0.933. Conclusion SDC1,IRF4, CD38,TNFRSF17 and CCND1 were up-regulated in multiple myeloma , and the combined diagnosis efficiency was high, which may be potential biomarkers of multiple myeloma , and provide new thoughts for future treatment.

参考文献/References:

[1] COOK G, MORRIS C T C M. Evolution or revolution in multiple myeloma therapy and the role of the UK[J].British Journal of Haematology, 2020, 191(4): 542-551.
[2] JURCZYSZYN A, WASZCZUK-GAJDA A , CASTILLO J J, et al. Primary refractory multiple myeloma:a real-world experience with 85 cases[J].Leukemia & Lymphoma, 2020, 61(12): 2868-2875.
[3] HUANG Junjie, CHAN S C, LOK V, et al. The epidemiological landscape of multiple myeloma: a global cancer registry estimate of disease burden, risk factors, and temporal trends[J]. Lancet Haematology, 2022, 9(9): e670-e677.
[4] GOODMAN A M, KIM M S, PRASAD V. Persistent challenges with treating multiple myeloma early[J].Blood, 2021, 137(4): 456-458.
[5] ARRON J R, CHOI Y. Bone versus immune system[J].Nature, 2000, 408(6812): 535-536.
[6] VAN ANDEL H, KOCEMBA K A, SPAARGAREN M, et al. Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options [J].Leukemia, 2019, 33(5): 1063-1075.
[7] PALUMBO A, ANDERSON K. Multiple myeloma[J]. New England Journal of Medicine, 2011, 364(11): 1046-1060.
[8] RAJKUMAR S V, KUMAR S. Multiple myeloma current treatment algorithms[J]. Blood Cancer Journal, 2020, 10(9): 94.
[9] 徐海燕, 陆学东.多发性骨髓瘤早期实验诊断相关新兴生物标志物的最新研究进展[J].现代检验医学杂志, 2021, 36(5): 180-183. XU Haiyan, LU Xuedong. Recent research rrogress of novel biomarkers for early experimental diagnosis of multiple myeloma[J]. Journal of Modern Laboratory Medicine, 2021, 36(5): 180-183.
[10] ZHAO Aiqi, KONG Fancong, LIU Chunjie, et al. Tumor cell-derived microvesicles induced not epithelial-mesenchymal transition but apoptosis in human proximal tubular(HK-2)cells:implications for renal impairment in multiple myeloma[J]. International Journal of Molecular Sciences, 2017, 18(3): 513.
[11] SUN Chuang, MAHENDRAVADA A, BALLARD B, et al. Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma[J]. Oncotarget, 2019, 10(24): 2369-2383.
[12] BAI Hua, WU Shuang, WANG Rong, et al. Bone marrow IRF4 level in multiple myeloma: an indicator of peripheral blood Th17 and disease[J]. Oncotarget, 2017, 8(49): 85392-85400.
[13] SHAFFER A L, EMRE N C T, LAMY L, et al. IRF4 addiction in multiple myeloma[J]. Nature, 2008, 454(7201): 226-231.
[14] 王天笑, 李群益, 施孝金, 等.CD38 及其单克隆抗体的研究进展[J]. 中国临床药学杂志, 2021, 30(3): 232-236. WANG Tianxiao, LI Qunyi, SHI Xiaojin, et al. Research progress of CD38 and its monoclonal antibody[J]. Chinese Journal of Clinical Pharmacy, 2021, 30(3): 232-236.
[15] YU Bo, JIANG Tianbo, LIU Delong. BCMA-targeted immunotherapy for multiple myeloma[J]. Journal of Hematology & Oncology, 2020, 13(1): 125.
[16] CASIMIRO M C, VELASCO-VEL?ZQUEZ M, AGUIRRE-ALVARADO C, et al. Overview of cyclins D1 function in cancer and the CDK inhibitor landscape: past and present[J]. Expert Opinion on Investigational Drugs, 2014, 23(3): 295-304.
[17] KUMAR S K, RAJKUMAR S V. The multiple myelomas-current concepts in cytogenetic classification and therapy[J]. Nature Reviews Clinical Oncology, 2018, 15(7): 409-421.
[18] AGNARELLI A, MITCHELL S, CAALIM G, et al. Dissecting the impact of bromodomain inhibitors on the interferon regulatory factor 4-MYC oncogenic axis in multiple myeloma[J]. Hematological Oncology, 2022, 40(3): 417-429.

相似文献/References:

[1]韩秀蕊,杨娣娣,李艳春,等.多发性骨髓瘤患者骨髓涂片与骨髓活检同步检查的比较分析[J].现代检验医学杂志,2015,30(03):129.[doi:10.3969/j.issn.1671-7414.2015.03.039]
 HAN Xiu-rui,YANG Di-di,LI Yan-chun,et al.Comparative Analysis of Bone Marrow Smears and Biopsies Synchronous Check for Myeloma Patients[J].Journal of Modern Laboratory Medicine,2015,30(05):129.[doi:10.3969/j.issn.1671-7414.2015.03.039]
[2]邱 爽,孟瑞芳,蒋筱漪,等.血清免疫固定电泳、蛋白电泳、免疫球蛋白及轻链定量在诊断多发性骨髓瘤中的临床应用[J].现代检验医学杂志,2015,30(02):61.[doi:10.3969/j.issn.1671-7414.2015.02.019]
 QIU Shuang,MENG Rui-fang,JIANG Xiao-yi,et al.Clinical Application of Immunofixtion Electrophoresis, Serum Protein Electrophoresis and Immunoglobulins and Light Chain Quantitative Analysis in the Diagnosis of Multiple Myeloma[J].Journal of Modern Laboratory Medicine,2015,30(05):61.[doi:10.3969/j.issn.1671-7414.2015.02.019]
[3]李 瑛,李 军.多发性骨髓瘤患者血清中IL-6与IL-27水平监测的临床应用[J].现代检验医学杂志,2016,31(04):87.[doi:10.3969/j.issn.16717-414.2016.04.023]
 LI Ying,LI Jun.Clinical Application of Monitoring IL-6 and IL-27 Levels in Patients with Multiple Myeloma[J].Journal of Modern Laboratory Medicine,2016,31(05):87.[doi:10.3969/j.issn.16717-414.2016.04.023]
[4]郭进京,胡林辉,陶千山,等.红细胞分布宽度在多发性骨髓瘤患者预后分期中的价值[J].现代检验医学杂志,2017,32(03):34.[doi:10.3969/j.issn.1671-7414.2017.03.009]
 GUO Jin-jing,HU Lin-hui,TAO Qian-shan,et al.Value of Red Cell Distribution Width in the Prognosis of Patients with Multiple Myeloma[J].Journal of Modern Laboratory Medicine,2017,32(05):34.[doi:10.3969/j.issn.1671-7414.2017.03.009]
[5]谭 奎,沈婵娟,张 玲,等.多发性骨髓瘤患者骨髓CD269和CD317基因的差异性表达研究[J].现代检验医学杂志,2017,32(06):64.[doi:10.3969/j.issn.1671-7414.2017.06.001]
 TAN Kui,SHEN Chan-juan,ZHANG Ling,et al.Differential Expression of CD269 and CD317 Genes in Bone Marrow of Patients with Multiple Myeloma[J].Journal of Modern Laboratory Medicine,2017,32(05):64.[doi:10.3969/j.issn.1671-7414.2017.06.001]
[6]盘国雄,谭才燕,何嘉颖,等.多发性骨髓瘤患者血清中lncRNA PCAT-1的表达水平与临床预后研究[J].现代检验医学杂志,2018,33(01):72.[doi:10.3969/j.issn.1671-7414.2018.01.001]
 PAN Guo-xiong,TAN Cai-yan,HE Jia-ying,et al.Serum LncRNA PCAT-1 Expression Level of Patients with Multiple Myeloma and Clinical Value[J].Journal of Modern Laboratory Medicine,2018,33(05):72.[doi:10.3969/j.issn.1671-7414.2018.01.001]
[7]刘玉霞,胡国瑜,袁朝晖,等.CD269和CD317在多发性骨髓瘤中的表达及临床意义[J].现代检验医学杂志,2018,33(02):58.[doi:10.3969/j.issn.1671-7414.2018.02.001]
 LIU Yu-xia,HU Guo-yu,YUAN Chao-hui,et al.Expression of CD269 and CD317 in Multiple Myeloma and Its Clinical Significance[J].Journal of Modern Laboratory Medicine,2018,33(05):58.[doi:10.3969/j.issn.1671-7414.2018.02.001]
[8]张 蓉,李国辉,刘小五,等.初诊多发性骨髓瘤患者外周血淋巴细胞绝对值/ 单核细胞绝对值比值在预测临床预后的价值研究[J].现代检验医学杂志,2020,35(01):101.[doi:10.3969/j.issn.1671-7414.2020.01.027]
 ZHANG Rong,LI Guo-hui,LIU Xiao-wu,et al.Value of Peripheral Blood Lymphocyte Absolute Value/Monocyte Absolute Value Ratio in Predicting Clinical Prognosis of Newly Diagnosed MultipleMyeloma Patients[J].Journal of Modern Laboratory Medicine,2020,35(05):101.[doi:10.3969/j.issn.1671-7414.2020.01.027]
[9]霍 豆,秦 爽,吴永昌,等.血清总轻链与游离轻链定量检测在多发性骨髓瘤诊断中的临床价值探讨[J].现代检验医学杂志,2020,35(04):87.[doi:10.3969/j.issn.1671-7414.2020.04.021]
 HUO Dou,QIN Shuang,WU Yong-chang,et al.Clinical Value of Quantitative Detection of sTLC and sFLC in Diagnosis of Multiple Myeloma[J].Journal of Modern Laboratory Medicine,2020,35(05):87.[doi:10.3969/j.issn.1671-7414.2020.04.021]
[10]何 进,张 艳,申娴娟,等.多发性骨髓瘤患者血清可溶性PD-L1水平在辅助诊断及临床分型的价值研究[J].现代检验医学杂志,2021,36(02):15.[doi:doi:10.3969/j.issn.1671-7414.2021.02.004]
 HE Jin,ZHANG Yan,SHEN Xian-juan,et al.Value of Blood Soluble PD-L1 in the Auxiliary Diagnosis and Clinical Subtype of Multiple Myeloma[J].Journal of Modern Laboratory Medicine,2021,36(05):15.[doi:doi:10.3969/j.issn.1671-7414.2021.02.004]

备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区科技支疆计划(2022E2056)。
作者简介:侯丽(1988-),女,硕士研究生,主管技师,主要从事临床检验诊断学及生物信息学,E-mail:sjyh135@qq.com。
通讯作者:朱有森(1969-),男,主任技师, 主要从事临床检验诊断学及分子生物学。
更新日期/Last Update: 2023-09-15