|
胎盘植入免疫关键基因的预测及生物信息学分析
|
Abstract:
目的:通过生物信息学方法预测胎盘植入疾病的关键免疫基因。方法:本研究在GEO数据库中选出数据集GSE189267,采用R语言软件(“limma”R包)对各组表达基因进行差异分析,筛选出有差异意义的差异表达基因(DEGs),随后通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)分析、加权基因表达网络分析(WGCNA)、蛋白质相互作用网络分析及基因集富集分析(GSEA)等生物信息学分析方法确定与胎盘植入性疾病显著相关的免疫基因。结果:共筛选出93个与胎盘植入性疾病高度相关的差异表达基因,通过WGCNA进一步鉴定出与穿透性胎盘植入显著相关的17个免疫相关基因。其中,瘦素(LEP)、绒毛膜生长激素1 (CSH1)、绒毛膜生长激素2 (CSH2)为前三个枢纽基因。对其分别进行单基因GSEA分析显示,LEP可能参与膜裂解、多泡体组织和核膜的重组,而CSH1和CSH2则参与了相似的生物过程,包括调节RAC蛋白信号转导和SRP依赖的共转译蛋白质膜定位。结论:本研究通过生物信息学方法提示LEP、CSH1和CSH2是穿透性胎盘植入的关键免疫基因,可能通过膜裂解、多泡体组织和核膜的重组、调节RAC蛋白信号转导和SRP依赖的共转译蛋白质膜定位等机制参与穿透性胎盘植入的发生,有助于更深入地理解穿透性胎盘植入,并为该疾病的潜在诊断和治疗靶点提供了进一步的见解。
Objective: To predict key immune-related genes in placental implantation disorders using bioinformatics methods. Methods: In this study, the dataset GSE189267 was selected from the GEO database. Differential expression analysis of genes in each group was performed using R software (“limma” R package) to identify differentially expressed genes (DEGs) with statistical significance. Subsequently, bioinformatics analysis methods, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction network analysis, and gene set enrichment analysis (GSEA), were employed to determine immune-related genes significantly associated with placental implantation disorders. Results: A total of 93 DEGs highly associated with placental implantation disorders were identified. Further analysis using WGCNA revealed 17 immune-related genes significantly associated with placenta percreta. Among them, leptin (LEP), chorionic somatomammotropin 1 (CSH1), and chorionic somatomammotropin 2 (CSH2) were identified as the top three hub genes. Single-gene GSEA analysis showed that LEP may be involved in membrane fission, multivesicular body organization, and nuclear membrane reorganization, while CSH1 and CSH2 were involved in similar biological processes, including regulation of RAC protein signal transduction and SRP-dependent cotranslational protein membrane targeting. Conclusion: This study suggests that LEP, CSH1, and CSH2 are key immune-related genes in placenta percreta. They may participate in the development of placenta percreta through mechanisms such as membrane fission, multivesicular body organization, nuclear membrane reorganization, regulation of RAC protein signal transduction, and SRP-dependent cotranslational protein membrane targeting. These findings help
[1] | 陈洪琴, 周容. 胎盘植入性疾病的分类及诊断[J]. 实用妇产科杂志, 2021, 37(1): 6-9. |
[2] | Conturie, C.L. and Lyell, D.J. (2022) Prenatal Diagnosis of Placenta Accreta Spectrum. Current Opinion in Obstetrics & Gynecology, 34, 90-99. https://doi.org/10.1097/gco.0000000000000773 |
[3] | Jauniaux, E., Kingdom, J.C. and Silver, R.M. (2021) A Comparison of Recent Guidelines in the Diagnosis and Management of Placenta Accreta Spectrum Disorders. Best Practice & Research Clinical Obstetrics & Gynaecology, 72, 102-116. https://doi.org/10.1016/j.bpobgyn.2020.06.007 |
[4] | 庞迤, 丘茜, 吴婉秋, 等. 产前彩超与MRI诊断植入型凶险性前置胎盘的应用价值[J]. 吉林医学, 2024, 45(2): 266-268. |
[5] | 张天玥. 胎盘植入谱系疾病血清生物标记物及超声标志物的临床研究[D]: [硕士学位论文]. 北京: 北京协和医学院, 2023. |
[6] | Ma, J., Liu, Y., Guo, Z., Sun, R., Yang, X., Zheng, W., et al. (2022) The Diversity of Trophoblast Cells and Niches of Placenta Accreta Spectrum Disorders Revealed by Single-Cell RNA Sequencing. Frontiers in Cell and Developmental Biology, 10, Article 1044198. https://doi.org/10.3389/fcell.2022.1044198 |
[7] | Chen, Y., Zou, P., Bu, C., Jiang, Q., Xue, L., Bao, J., et al. (2023) Upregulated CXCL8 in Placenta Accreta Spectruma Regulates the Migration and Invasion of HTR-8/SVneo Cells. Molecular Biology Reports, 50, 8189-8199. https://doi.org/10.1007/s11033-023-08669-x |
[8] | Silver, R.M. and Branch, D.W. (2018) Placenta Accreta Spectrum. New England Journal of Medicine, 378, 1529-1536. https://doi.org/10.1056/nejmcp1709324 |
[9] | Timofeeva, A.V., Fedorov, I.S., Suhova, Y.V., Tarasova, A.M., Ezhova, L.S., Zabelina, T.M., et al. (2024) Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening. International Journal of Molecular Sciences, 25, Article 871. https://doi.org/10.3390/ijms25020871 |
[10] | 李琴华, 侯丽辉, 吴效科. 生长激素和胰岛素样生长因子-Ⅰ对生殖的影响[J]. 中国妇幼健康研究, 2007, 18(6): 525-528. |
[11] | 卢丹, 祝淡抹, 单委, 等. 胰岛素样生长因子和胰岛素样生长因子结合蛋白-3与胎儿生长受限的关系[J]. 中国医药科学, 2021, 11(4): 9-12. |
[12] | 查红英, 袁庆新. 妊娠期糖尿病母体胎盘激素和能量代谢改变的研究进展[J]. 实用妇产科杂志, 2023, 39(6): 425-429. |
[13] | Wen, B., Liao, H., Lin, W., Li, Z., Ma, X., Xu, Q., et al. (2023) The Role of TGF-β during Pregnancy and Pregnancy Complications. International Journal of Molecular Sciences, 24, Article 16882. https://doi.org/10.3390/ijms242316882 |
[14] | Hashimoto, K., Miyagawa, Y., Watanabe, S., Takasaki, K., Nishizawa, M., Yatsuki, K., et al. (2023) The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta. International Journal of Molecular Sciences, 24, Article 13706. https://doi.org/10.3390/ijms241813706 |
[15] | Khamoushi, T., Ahmadi, M., Ali-Hassanzadeh, M., Zare, M., Hesampour, F., Gharesi-Fard, B., et al. (2020) Evaluation of Transforming Growth Factor-Β1 and Interleukin-35 Serum Levels in Patients with Placenta Accreta. Laboratory Medicine, 52, 245-249. https://doi.org/10.1093/labmed/lmaa071 |
[16] | Adu-Gyamfi, E.A., Czika, A., Gorleku, P.N., Ullah, A., Panhwar, Z., Ruan, L., et al. (2020) The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation. Reproductive Sciences, 28, 305-320. https://doi.org/10.1007/s43032-020-00364-7 |
[17] | 赵亮, 张蕾, 孙丽芳, 等. 辅助生殖胎盘JAK-STAT信号通路研究[J]. 中国优生与遗传杂志, 2018, 26(9): 96-104. |
[18] | 余樱, 范翠芳. 胰岛素增强子结合蛋白通过影响PI3K/AKT信号通路参与滋养细胞血管形成的研究[J]. 中国性科学, 2022, 31(11): 95-99. |
[19] | de Knegt, V.E., Hedley, P.L., Kanters, J.K., Thagaard, I.N., Krebs, L., Christiansen, M., et al. (2021) The Role of Leptin in Fetal Growth during Pre-Eclampsia. International Journal of Molecular Sciences, 22, Article 4569. https://doi.org/10.3390/ijms22094569 |
[20] | 张玲, 陈萱. 瘦素、内脂素与妊娠期高血压疾病关系的研究进展[J]. 现代医学, 2014, 42(6): 700-702. |
[21] | 樊春云, 杨明珠, 祝玉芳, 等. 胎盘植入孕妇子宫动脉血流动力学参数与血管新生的关系及其相关指标诊断价值[J]. 血管与腔内血管外科杂志, 2024, 10(2): 219-223. |
[22] | 程玉梅, 阴赪宏. 胎盘生物标志物与妊娠疾病相关性的研究进展[J]. 北京医学, 2023, 45(2): 147-150. |
[23] | Li, R., Zhou, C., Ye, K., Chen, H. and Peng, M. (2025) Identification of Genes Involved in Energy Metabolism in Preeclampsia and Discovery of Early Biomarkers. Frontiers in Immunology, 16, Article 1496046. https://doi.org/10.3389/fimmu.2025.1496046 |
[24] | Tanner, A.R., Lynch, C.S., Kennedy, V.C., Ali, A., Winger, Q.A., Rozance, P.J., et al. (2021) CSH RNA Interference Reduces Global Nutrient Uptake and Umbilical Blood Flow Resulting in Intrauterine Growth Restriction. International Journal of Molecular Sciences, 22, Article 8150. https://doi.org/10.3390/ijms22158150 |
[25] | Saso, J., Shields, S., Zuo, Y. and Chakraborty, C. (2012) Role of Rho GTPases in Human Trophoblast Migration Induced by IGFBP11. Biology of Reproduction, 86, 1-9. https://doi.org/10.1095/biolreprod.111.094698 |
[26] | Schibich, D., Gloge, F., Pöhner, I., Björkholm, P., Wade, R.C., von Heijne, G., et al. (2016) Global Profiling of SRP Interaction with Nascent Polypeptides. Nature, 536, 219-223. https://doi.org/10.1038/nature19070 |