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BGN基因在膀胱癌进展与转移中的作用机制研究
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Abstract:
目的：探讨双糖链蛋白聚糖(BGN)基因在膀胱癌进展与转移中的作用机制及与免疫浸润的关系。方法：收集TCGA数据库关于BGN的数据信息并利用R语言及SPSS进行统计分析。运用TIMER 2.0数据库分析BGN与免疫细胞浸润的关系。结果：利用TCGA数据库进行分析显示，与癌旁组织相比，BGN在膀胱癌组织中呈高表达(P < 0.05)，且在人种、性别、病理学分期中等不同亚组表达中具有统计学差异(P < 0.05)。BGN的表达与巨噬细胞、NK细胞、B细胞、DC细胞、Treg细胞等多种免疫细胞呈正相关。富集分析显示其在膀胱中的表达可能与G蛋白偶联受体、中性粒细胞脱颗粒信号通路相关。结论：BGN在膀胱癌组织中高表达，且与膀胱癌预后显著相关，与免疫浸润相关，可能为膀胱癌基因治疗提供新的靶点及更新免疫学说理论。
Objective: To investigate the mechanism of BGN gene in the progression and metastasis of bladder cancer and its relationship with immune invasion. Methods: The data information about BGN in TCGA database were collected and analyzed by R language and SPSS. TIMER 2.0 database was used to analyze the relationship between BGN and immune cell infiltration. Results: TCGA database analysis showed that BGN was highly expressed in bladder cancer tissues compared with adjacent tissues (P < 0.05), and there were statistical differences in different subgroups such as race, gender and pathological stage (P < 0.05). The expression of BGN was positively correlated with macrophag-es, NK cells, B cells, DC cells, Treg cells and other immune cells. Enrichment analysis showed that its expression in bladder may be closely related to G protein-coupled receptor and neutrophil degran-ulation signaling pathway. Conclusion: BGN is highly expressed in bladder cancer tissues, and is sig-nificantly associated with the prognosis of bladder cancer, and is associated with immune invasion. BGN may provide a new target for gene therapy of bladder cancer and update immune theory.
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https://doi.org/10.1001/jama.2020.17598 |
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https://doi.org/10.1007/s11010-021-04216-z |
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https://doi.org/10.1016/j.ccell.2020.09.015 |
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https://doi.org/10.1111/febs.14791 |
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https://doi.org/10.1172/JCI23755 |
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| [18] | Edwards, I.J. (2012) Proteoglycans in Prostate Cancer. Nature Reviews Urology, 9, 196-206.
https://doi.org/10.1038/nrurol.2012.19 |
| [19] | Liu, Y., Li, W., Li, X., et al. (2014) Expression and Significance of Bi-glycan in Endometrial Cancer. Archives of Gynecology and Obstetrics, 289, 649-655. https://doi.org/10.1007/s00404-013-3017-3 |
| [20] | Baghy, K., Tátrai, P., Reg？s, E., et al. (2016) Proteoglycans in Liver Cancer. World Journal of Gastroenterology, 22, 379-393. https://doi.org/10.3748/wjg.v22.i1.379 |
| [21] | Maishi, N. and Hida, K. (2017) Tumor Endothelial Cells Accelerate Tumor Metastasis. Cancer Science, 108, 1921- 1926. https://doi.org/10.1111/cas.13336 |
| [22] | Manupati, K., Paul, R., Hao, M., et al. (2022) Biglycan Promotes Cancer Stem Cell Properties, NFkappaB Signaling and Metastatic Potential in Breast Cancer Cells. Cancers, 14, 455. https://doi.org/10.3390/cancers14020455 |
| [23] | [1] Lenis, A.T., Lec, P.M., Chamie, K., et al. (2020) Bladder Cancer: A Review. JAMA, 324, 1980-1991.
https://doi.org/10.1001/jama.2020.17598 |
| [24] | Robertson, A.G., Kim, J., Al-Ahmadie, H., et al. (2018) Compre-hensive Molecular Characterization of Muscle-Inva- sive Bladder Cancer. Cell, 174, 1033. https://doi.org/10.1016/j.cell.2018.07.036 |
| [25] | Appunni, S., Rubens, M., Ramamoorthy, V., et al. (2021) Biglycan: An Emerging Small Leucine-Rich Proteoglycan (SLRP) Marker and Its Clinicopathological Significance. Molecular and Cellular Biochemistry, 476, 3935-3950.
https://doi.org/10.1007/s11010-021-04216-z |
| [26] | 孙恒子. 双糖链蛋白聚糖Biglycan在子宫内膜癌进展中的作用研究[D]: [硕士学位论文]. 济南: 山东大学, 2016. |
| [27] | Zhou, Y., Bian, S., Zhou, X., et al. (2020) Single-Cell Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer. Cancer Cell, 38, 818-828.e5.
https://doi.org/10.1016/j.ccell.2020.09.015 |
| [28] | Niedworok, C., Rock, K., Kretschmer, I., et al. (2013) Inhibitory Role of the Small Leucine-Rich Proteoglycan Biglycan in Bladder Cancer. PLOS ONE, 8, e80084. https://doi.org/10.1371/journal.pone.0080084 |
| [29] | Schulz, G.B., Grimm, T., Sers, C., et al. (2019) Prognostic Value and Association with Epithelial-Mesenchymal Transition and Molecular Subtypes of the Proteoglycan Biglycan in Advanced Bladder Cancer. Urologic Oncology, 37, 530.e9-e18. https://doi.org/10.1016/j.urolonc.2019.05.011 |
| [30] | 黄楠, 邓红彬. 膀胱癌肿瘤微环境中抑制性免疫浸润细胞的研究进展[J]. 现代医药卫生, 2021, 37(17): 2966-2971. |
| [31] | 宋启斌, 褚玉新, 胡钦勇. 肿瘤微环境变化在肿瘤免疫耐受中的作用[J]. 中国肿瘤, 2016, 25(10): 794-798. |
| [32] | 卫阳兵, 闫鹏宇, 杨晓峰. 肿瘤微环境在膀胱癌发生发展中的作用机制[J]. 生命的化学, 2022, 42(9): 1665-1671. |
| [33] | 胡雪. 膀胱癌肿瘤微环境中免疫细胞的浸润模式及其临床意义[D]: [硕士学位论文]. 天津: 天津医科大学, 2020. |
| [34] | Barocas, D.A., Boorjian, S.A., Alvarez, R.D., et al. (2020) Microhematuria: AUA/SUFU Guideline. The Journal of Urology, 204, 778-786. https://doi.org/10.1097/JU.0000000000001297 |
| [35] | Schaefer, L. and Iozzo, R.V. (2008) Biological Functions of the Small Leucine-Rich Proteoglycans: From Genetics to Signal Transduction. Journal of Biological Chemistry, 283, 21305-21309. https://doi.org/10.1074/jbc.R800020200 |
| [36] | Roedig, H., Nastase, M.V., Wygrecka, M., et al. (2019) Breaking down Chronic Inflammatory Diseases: The Role of Biglycan in Promoting a Switch between Inflamma-tion and Autophagy. The FEBS Journal, 286, 2965-2979.
https://doi.org/10.1111/febs.14791 |
| [37] | Schaefer, L., Babelova, A., Kiss, E., et al. (2005) The Matrix Component Biglycan Is Proinflammatory and Signals through Toll-Like Receptors 4 and 2 in Macrophages. The Journal of Clinical Investigation, 115, 2223-2233.
https://doi.org/10.1172/JCI23755 |
| [38] | 赵浚江, 刘皓, 郑自文, 等. BGN基因在胃癌中的表达及与预后相关性[J]. 青岛大学学报(医学版), 2022, 58(4): 500-504. |
| [39] | Pinto, F., Santos-Ferreira, L., Pinto, M.T., et al. (2021) The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness. Cancers, 13, 1330. https://doi.org/10.3390/cancers13061330 |
| [40] | Edwards, I.J. (2012) Proteoglycans in Prostate Cancer. Nature Reviews Urology, 9, 196-206.
https://doi.org/10.1038/nrurol.2012.19 |
| [41] | Liu, Y., Li, W., Li, X., et al. (2014) Expression and Significance of Bi-glycan in Endometrial Cancer. Archives of Gynecology and Obstetrics, 289, 649-655. https://doi.org/10.1007/s00404-013-3017-3 |
| [42] | Baghy, K., Tátrai, P., Reg？s, E., et al. (2016) Proteoglycans in Liver Cancer. World Journal of Gastroenterology, 22, 379-393. https://doi.org/10.3748/wjg.v22.i1.379 |
| [43] | Maishi, N. and Hida, K. (2017) Tumor Endothelial Cells Accelerate Tumor Metastasis. Cancer Science, 108, 1921- 1926. https://doi.org/10.1111/cas.13336 |
| [44] | Manupati, K., Paul, R., Hao, M., et al. (2022) Biglycan Promotes Cancer Stem Cell Properties, NFkappaB Signaling and Metastatic Potential in Breast Cancer Cells. Cancers, 14, 455. https://doi.org/10.3390/cancers14020455 |
