|
|
VPS72在肝细胞癌中的预后意义及其与免疫浸润的相关性的生物信息学分析
|
Abstract:
背景：VPS72是EP400和Snf2相关的CBP激活蛋白(SRCAP)染色质重塑复合物的组成部分。目前，VPS72在肝细胞癌(Hepatocellular Carcinoma, LIHC)中的预后价值尚不明确。方法：本研究利用ONCOMINE、UALCAN、GEPIA、STRING和TIMER等多个公共数据库，系统分析了VPS72在肝细胞癌中的表达特征及其临床意义。结果：分析后发现，在肝细胞癌(LIHC)中，VPS72的过表达与临床分期和病理分级显著相关，且其mRNA高表达与患者总生存期缩短密切相关。此外，VPS72启动子区在肝癌中存在明显的高甲基化改变。进一步分析显示，VPS72的表达与LIHC中B细胞、CD4？ T细胞、CD8？ T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平呈显著正相关。最后通过STRING数据库还构建了VPS72的蛋白质相互作用网络。结论：VPS72可能作为LIHC患者预后判断和免疫治疗靶点的潜在生物标志物。
Background: VPS72 forms part of the EP400 and Snf2-related CBP-activator protein (SRCAP) chromatin remodeling complexes. The prognostic value of VPS72 in hepatocellular carcinoma is not known. Methods: We used the ONCOMINE, UALCAN, GEPIA, STRING and TIMER databases to study the expression of VPS72 in hepatocellular carcinoma and its medical significance. Results: Analysis revealed that VPS72 overexpression was markedly correlated with both clinical stage and pathological grade in Liver hepatocellular carcinoma (LIHC), and that higher mRNA expression of VPS72 was significantly related to shorter overall survival. Moreover, we observed significant differences in the hypermethylation of the VPS72 promoter in liver cancer. Furthermore, we identified significant correlations between the expression of VPS72 and the infiltration of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in LIHC. Finally, a protein interaction network for VPS72 was constructed using the STRING database. Conclusion: VPS72 may be useful as a prognostic biomarker and immunotherapeutic target in LIHC patients.
| [1] | Anwanwan, D., Singh, S.K., Singh, S., Saikam, V. and Singh, R. (2020) Challenges in Liver Cancer and Possible Treatment Approaches. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1873, Article 188314. https://doi.org/10.1016/j.bbcan.2019.188314 |
| [2] | El-Serag, H.B. (2011) Hepatocellular Carcinoma. New England Journal of Medicine, 365, 1118-1127. https://doi.org/10.1056/NEJMra1001683 |
| [3] | Mokdad, A.A., Singal, A.G. and Yopp, A.C. (2016) Treatment of Liver Cancer. JAMA, 315, Article 100. https://doi.org/10.1001/jama.2015.15431 |
| [4] | Pittala, S., Krelin, Y. and Shoshan-Barmatz, V. (2018) Targeting Liver Cancer and Associated Pathologies in Mice with a Mitochondrial Vdac1-Based Peptide. Neoplasia, 20, 594-609. https://doi.org/10.1016/j.neo.2018.02.012 |
| [5] | Xiao, Y., Lin, M., Jiang, X., Ye, J., Guo, T., Shi, Y., et al. (2017) The Recent Advances on Liver Cancer Stem Cells: Biomarkers, Separation, and Therapy. Analytical Cellular Pathology, 2017, Article ID: 5108653. https://doi.org/10.1155/2017/5108653 |
| [6] | Latrick, C.M., Marek, M., Ouararhni, K., Papin, C., Stoll, I., Ignatyeva, M., et al. (2016) Molecular Basis and Specificity of H2A.Z-H2B Recognition and Deposition by the Histone Chaperone Yl1. Nature Structural & Molecular Biology, 23, 309-316. https://doi.org/10.1038/nsmb.3189 |
| [7] | Liang, X., Shan, S., Pan, L., Zhao, J., Ranjan, A., Wang, F., et al. (2016) Structural Basis of H2A.Z Recognition by SRCAP Chromatin-Remodeling Subunit Yl1. Nature Structural & Molecular Biology, 23, 317-323. https://doi.org/10.1038/nsmb.3190 |
| [8] | Rhodes, D.R., Yu, J., Shanker, K., Deshpande, N., Varambally, R., Ghosh, D., et al. (2004) ONCOMINE: A Cancer Microarray Database and Integrated Data-Mining Platform. Neoplasia, 6, 1-6. https://doi.org/10.1016/S1476-5586(04)80047-2 |
| [9] | Chandrashekar, D.S., Bashel, B., Balasubramanya, S.A.H., Creighton, C.J., Ponce-Rodriguez, I., Chakravarthi, B.V.S.K., et al. (2017) UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19, 649-658. https://doi.org/10.1016/j.neo.2017.05.002 |
| [10] | Tang, Z., Li, C., Kang, B., Gao, G., Li, C. and Zhang, Z. (2017) GEPIA: A Web Server for Cancer and Normal Gene Expression Profiling and Interactive Analyses. Nucleic Acids Research, 45, W98-W102. https://doi.org/10.1093/nar/gkx247 |
| [11] | Li, T., Fan, J., Wang, B., Traugh, N., Chen, Q., Liu, J.S., et al. (2017) TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Research, 77, e108-e110. https://doi.org/10.1158/0008-5472.CAN-17-0307 |
| [12] | Szklarczyk, D., Gable, A.L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., et al. (2018) STRING V11: Protein-Protein Association Networks with Increased Coverage, Supporting Functional Discovery in Genome-Wide Experimental Datasets. Nucleic Acids Research, 47, D607-D613. https://doi.org/10.1093/nar/gky1131 |
| [13] | Hartke, J., Johnson, M. and Ghabril, M. (2017) The Diagnosis and Treatment of Hepatocellular Carcinoma. Seminars in Diagnostic Pathology, 34, 153-159. https://doi.org/10.1053/j.semdp.2016.12.011 |
| [14] | Zhao, J., Fu, Y., Wu, J., Li, J., Huang, G. and Qin, L. (2018) The Diverse Mechanisms of MiRNAs and LNCRNAs in the Maintenance of Liver Cancer Stem Cells. BioMed Research International, 2018, Article ID: 8686027. https://doi.org/10.1155/2018/8686027 |
| [15] | Kihn-Alarcón, A.J., Toledo-Ponce, M.F., Velarde, A. and Xu, X. (2019) Liver Cancer in Guatemala: An Analysis of Mortality and Incidence Trends from 2012 to 2016. Journal of Global Oncology, 5, 1-8. https://doi.org/10.1200/JGO.18.00179 |
| [16] | Moreno-Andrés, D., Yokoyama, H., Scheufen, A., Holzer, G., Lue, H., Schellhaus, A.K., et al. (2020) Vps72/yl1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis. Cells, 9, Article 1702. https://doi.org/10.3390/cells9071702 |
| [17] | Horikawa, I., Tanaka, H., Yuasa, Y., Suzuki, M. and Oshimura, M. (1995) Molecular Cloning of a Novel Human cDNA on Chromosome 1q21 and Its Mouse Homolog Encoding a Nuclear Protein with DNA-Binding Ability. biochemical and Biophysical Research Communications, 208, 999-1007. https://doi.org/10.1006/bbrc.1995.1433 |
| [18] | Horikawa, I., Tanaka, H., Yuasa, Y., Suzuki, M., Shimizu, M. and Oshimura, M. (1995) Forced Expression of YL-1 Protein Suppresses the Anchorage-Independent Growth of Kirsten Sarcoma Virus-Transformed NIH3T3 Cells. Experimental Cell Research, 220, 11-17. https://doi.org/10.1006/excr.1995.1286 |
| [19] | Wherry, E.J. (2011) T Cell Exhaustion. Nature Immunology, 12, 492-499. https://doi.org/10.1038/ni.2035 |
