基于生物信息学识别和分析慢性鼻窦炎新的生物标志物
Identification and Analysis of Novel Biomarkers for Chronic Sinusitis Based on Bioinformatics
DOI: 10.12677/hjbm.2025.154074, PDF,   
作者: 刘 聪：大理大学临床医学院，云南 大理；毛春鹏：昆明医科大学公共卫生学院，云南 昆明；陈银忠*：大理大学第一附属医院耳鼻咽喉头颈外科，云南 大理
关键词: 慢性鼻窦炎；生物标志物；治疗靶点；生物信息学；GEO数据库；差异表达基因；加权基因共表达网络分析；Chronic Rhinosinusitis； Biomarker； Therapeutic Target； Bioinformatics； GEO Database； DEGs； WGCNA
摘要: 目的：采用生物信息学方法系统筛选慢性鼻窦炎(CRS)的新型治疗靶点。方法：从GEO数据库获取GSE36830、GSE179265和GSE136825三个独立数据集，分别对其进行差异表达分析并得到差异表达基因(DEGs)，对DEGs进行GO功能注释和KEGG通路富集分析，整合Cytoscape软件的cytoHubba插件和加权基因共表达网络(WGCNA)分析筛选关键基因，在GSE136825数据集中验证关键基因的表达情况。结果：三个数据集分别鉴定出428、1896和1263个DEGs，富集分析表示这些基因显著富集于免疫相关通路。WGCNA分析确定蓝绿色模块(turquoise module)与CRS相关性最高，筛选出7个核心基因：CD209、CD86、CSF1R、IL2RA、ITGAM、SIGLEC1和CD33。结论：CD209、CD86、CSF1R、IL2RA、ITGAM、SIGLEC1参与了CRS疾病的发病机制，且CD209、IL2RA、SIGLEC1具有作为CRS诊断标志物和靶向治疗靶点的潜力，为CRS的诊断标志物和治疗靶点。
Abstract: Objective: To systematically identify novel therapeutic targets for chronic rhinosinusitis (CRS) using bioinformatics approaches. Methods: Three independent datasets (GSE36830, GSE179265, and GSE136825) were obtained from the GEO database. Differential expression analysis was performed to identify differentially expressed genes (DEGs). Functional annotation (GO) and pathway enrichment (KEGG) analyses were conducted on the DEGs. Key genes were screened by integrating the cytoHubba plugin in Cytoscape and weighted gene co-expression network analysis (WGCNA). The expression patterns of key genes were validated in the GSE136825 dataset. Results: A total of 428, 1896, and 1263 DEGs were identified in the three datasets, respectively. Enrichment analysis revealed that these genes were significantly associated with immune-related pathways. WGCNA identified the turquoise module as the most correlated with CRS, leading to the selection of 7 core genes: CD209, CD86, CSF1R, IL2RA, ITGAM, SIGLEC1, and CD33. Conclusion: CD209, CD86, CSF1R, IL2RA, ITGAM, and SIGLEC1 are involved in the pathogenesis of CRS. CD209, IL2RA, and SIGLEC1 show potential as diagnostic biomarkers and targeted therapeutic candidates for CRS.
文章引用：刘聪, 毛春鹏, 陈银忠. 基于生物信息学识别和分析慢性鼻窦炎新的生物标志物[J]. 生物医学, 2025, 15(4): 665-680. https://doi.org/10.12677/hjbm.2025.154074

参考文献

[1] Szaleniec, J., Górski, A., Szaleniec, M., Międzybrodzki, R., Weber-Dąbrowska, B., Stręk, P., et al. (2017) Can Phage Therapy Solve the Problem of Recalcitrant Chronic Rhinosinusitis? Future Microbiology, 12, 1427-1442. [Google Scholar] [CrossRef] [PubMed]
[2] Kim, J., Ko, I., Kim, M.S., Kim, D.W., Cho, B. and Kim, D. (2020) Relationship of Chronic Rhinosinusitis with Asthma, Myocardial Infarction, Stroke, Anxiety, and Depression. The Journal of Allergy and Clinical Immunology: In Practice, 8, 721-727.E3. [Google Scholar] [CrossRef] [PubMed]
[3] Waters, E.M., Neill, D.R., Kaman, B., Sahota, J.S., Clokie, M.R.J., Winstanley, C., et al. (2017) Phage Therapy Is Highly Effective against Chronic Lung Infections Withpseudomonas Aeruginosa. Thorax, 72, 666-667. [Google Scholar] [CrossRef] [PubMed]
[4] Okano, M., Kariya, S., Ohta, N., et al. (2015) Association and Management of Eosinophilic Inflammation in Upper and Lower Airways. Allergology International, 64, 131-138. [Google Scholar] [CrossRef] [PubMed]
[5] Calus, L., Van Bruaene, N., Bosteels, C., Dejonckheere, S., Van Zele, T., Holtappels, G., et al. (2019) Twelve-Year Follow-up Study after Endoscopic Sinus Surgery in Patients with Chronic Rhinosinusitis with Nasal Polyposis. Clinical and Translational Allergy, 9, Article No. 30. [Google Scholar] [CrossRef] [PubMed]
[6] DeConde, A.S., Mace, J.C., Levy, J.M., Rudmik, L., Alt, J.A. and Smith, T.L. (2016) Prevalence of Polyp Recurrence after Endoscopic Sinus Surgery for Chronic Rhinosinusitis with Nasal Polyposis. The Laryngoscope, 127, 550-555. [Google Scholar] [CrossRef] [PubMed]
[7] Bachert, C., Han, J.K., Wagenmann, M., Hosemann, W., Lee, S.E., Backer, V., et al. (2021) EUFOREA Expert Board Meeting on Uncontrolled Severe Chronic Rhinosinusitis with Nasal Polyps (CRSWNP) and Biologics: Definitions and Management. Journal of Allergy and Clinical Immunology, 147, 29-36. [Google Scholar] [CrossRef] [PubMed]
[8] Hopkins, C. (2019) Chronic Rhinosinusitis with Nasal Polyps. New England Journal of Medicine, 381, 55-63. [Google Scholar] [CrossRef] [PubMed]
[9] Łusiak-Szelachowska, M., Żaczek, M., Weber-Dąbrowska, B., et al. (2014) Phage Neutralization by Sera of Patients Receiving Phage Therapy. Viral Immunology, 27, 295-304. [Google Scholar] [CrossRef] [PubMed]
[10] Stevens, W.W., Ocampo, C.J., Berdnikovs, S., Sakashita, M., Mahdavinia, M., Suh, L., et al. (2015) Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-Exacerbated Respiratory Disease. American Journal of Respiratory and Critical Care Medicine, 192, 682-694. [Google Scholar] [CrossRef] [PubMed]
[11] Nakayama, T., Lee, I.T., Le, W., Tsunemi, Y., Borchard, N.A., Zarabanda, D., et al. (2022) Inflammatory Molecular Endotypes of Nasal Polyps Derived from White and Japanese Populations. Journal of Allergy and Clinical Immunology, 149, 1296-1308.E6. [Google Scholar] [CrossRef] [PubMed]
[12] Peng, Y., Zi, X.X., Tian, T.F., et al. (2019) Whole-Transcriptome Sequencing Reveals Heightened Inflammation and Defective Host Defence Responses in Chronic Rhinosinusitis with Nasal Polyps. European Respiratory Journal, 54, Article 1900732. [Google Scholar] [CrossRef] [PubMed]
[13] 贾忆莲, 聂佳妮, 王洪敏, 等. NCF2在慢性鼻窦炎伴鼻息肉中的相关性研究[J]. 临床耳鼻咽喉头颈外科杂志, 2024, 38(4): 303-309.
[14] 祝旭清, 王国祥, 王建文, 等. 幽门螺杆菌感染患者外周血细胞因子的改变及临床意义[J]. 中华医院感染学杂志, 2016, 26(17): 3878-3880.
[15] Sugano, K., Tack, J., Kuipers, E.J., Graham, D.Y., El-Omar, E.M., Miura, S., et al. (2015) Kyoto Global Consensus Report on Helicobacter pylorigastritis. Gut, 64, 1353-1367. [Google Scholar] [CrossRef] [PubMed]
[16] Aydillo, T., Gonzalez-Reiche, A.S., Aslam, S., et al. (2020) Shedding of Viable SARS-CoV-2 after Immunosuppres-sive Therapy for Cancer. New England Journal of Medicine, 383, 2586-2588. [Google Scholar] [CrossRef] 
[17] Liu, P., Ridilla, M., Patel, P., Betts, L., Gallichotte, E., Shahidi, L., et al. (2017) Beyond Attachment: Roles of DC-SIGN in Dengue Virus Infection. Traffic, 18, 218-231. [Google Scholar] [CrossRef] [PubMed]
[18] Noll, A.J., Yu, Y., Lasanajak, Y., Duska-McEwen, G., Buck, R.H., Smith, D.F., et al. (2016) Human DC-SIGN Binds Specific Human Milk Glycans. Biochemical Journal, 473, 1343-1353. [Google Scholar] [CrossRef] [PubMed]
[19] Hottz, E.D., Oliveira, M.F., Nunes, P.C.G., Nogueira, R.M.R., Valls-de-Souza, R., Da Poian, A.T., et al. (2013) Dengue Induces Platelet Activation, Mitochondrial Dysfunction and Cell Death through Mechanisms That Involve DC-SIGN and Caspases. Journal of Thrombosis and Haemostasis, 11, 951-962. [Google Scholar] [CrossRef] [PubMed]
[20] Yu, X., Vasiljevic, S., Mitchell, D.A., Crispin, M. and Scanlan, C.N. (2013) Dissecting the Molecular Mechanism of IVIG Therapy: The Interaction between Serum Igg and DC-SIGN Is Independent of Antibody Glycoform or Fc Domain. Journal of Molecular Biology, 425, 1253-1258. [Google Scholar] [CrossRef] [PubMed]
[21] Schwartz, A.M., Demin, D.E., Vorontsov, I.E., et al. (2017) Multiple Single Nucleotide Polymorphisms in the First Intron of the IL2RA Gene affect Transcription Factor Binding and Enhancer Activity. Gene, 602, 50-56. [Google Scholar] [CrossRef] [PubMed]
[22] Redler, S., Albert, F., Brockschmidt, F.F., et al. (2012) Investigation of Selected Cytokine Genes Suggests that IL2RA and the TNF/LTA Locus Are Risk Factors for Severe Alopecia Areata. British Journal of Dermatology, 167, 1360-1365. [Google Scholar] [CrossRef] [PubMed]
[23] 江莉, 吴晓君, 黄俊彬, 等. IL2RA, IL-10基因单核苷酸多态性与儿童EBV-HLH相关性的研究[J]. 中国实验血液学杂志, 2020, 28(2): 646-651.
[24] Dhawan, M., Rabaan, A.A., Alwarthan, S., Alhajri, M., Halwani, M.A., Alshengeti, A., et al. (2023) Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long Covid. Vaccines, 11, Article 699. [Google Scholar] [CrossRef] [PubMed]
[25] Hartnell, A., Steel, J., Turley, H., Jones, M., Jackson, D.G. and Crocker, P.R. (2001) Characterization of Human Sialoadhesin, a Sialic Acid Binding Receptor Expressed by Resident and Inflammatory Macrophage Populations. Blood, 97, 288-296. [Google Scholar] [CrossRef] [PubMed]
[26] Zheng, Q., Hou, J., Zhou, Y., et al. (2015) Siglec1 Suppresses Antiviral Innate Immune Response by Inducing TBK1 Degradation via the Ubiquitin Ligase TRIM27. Cell Research, 25, 1121-1136. [Google Scholar] [CrossRef] [PubMed]
[27] Qian, Y., Yang, T., Liang, H. and Deng, M. (2022) Myeloid Checkpoints for Cancer Immunotherapy. Chinese Journal of Cancer Research, 34, 460-482. [Google Scholar] [CrossRef] [PubMed]
[28] Singh, R. and Choi, B.K. (2019) Siglec1-Expressing Subcapsular Sinus Macrophages Provide Soil for Melanoma Lymph Node Metastasis. eLife, 8, e48916. [Google Scholar] [CrossRef] 

为你推荐