生物信息学方法探讨VPS72在肺腺/鳞癌中的表达及潜在作用机制

doi:10.6040/j.issn.1671-7554.0.2022.1243

摘要/Abstract

摘要： 目的通过多种数据库分析空泡蛋白72同源物(VPS72)在肺腺/鳞癌中的表达水平、预后关系及潜在作用机制。方法基于肿瘤基因组图谱(TCGA)的数据集结合TIMER数据库和R语言数据包分析VPS72在肺腺/鳞癌的表达水平,Kaplan-Meier Plotter结合ROC曲线在线软件评估VPS72的预后关系和诊断价值,采用STRING和LinkedOmics筛选VPS72的互作蛋白和共表达基因,并通过LinkedOmics进行GO/KEGG功能富集分析,利用TIMER分析VPS72的表达与免疫细胞浸润之间的相关性,通过TISIDB数据库分析VPS72表达与不同免疫亚型的相关性。结果 VPS72在肺腺/鳞癌中高表达,高表达VPS72的肺腺癌患者总生存期明显缩短(P=0.01),但高表达VPS72的肺鳞癌患者总生存期差异无统计学意义(P=0.17)。PPI分析发现,VPS72与H2AFZ、RUVBL1、DMAP1等10个蛋白存在相互作用。功能富集分析发现,VPS72主要参与剪接体和核糖体合成等过程。在肺腺癌中,VPS72表达与多种免疫细胞(包括B细胞、CD8+T细胞、CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞)浸润呈负相关;在肺鳞癌中,VPS72表达与巨噬细胞和中性粒细胞呈负相关。在肺腺/鳞癌中,VPS72表达与6种免疫亚型相关。结论 VPS72在肺腺/鳞癌中表达显著增高,与肺腺癌的预后有一定的相关性,且参与了多种通路过程,与多种免疫细胞具有相关性,可能成为肺腺/鳞癌预后预测和治疗的新靶点。

关键词: 肺腺癌, 肺鳞癌, 空泡蛋白72同源物, 肿瘤基因组图谱, 免疫浸润

Abstract: Objective To explore the expression, prognostic relationship and potential mechanism of vacuolar protein sorting 72 homolog(VPS72)in lung adenocarcinoma/squamous cell carcinoma using multiple databases. Methods The expression level of VPS72 in lung adenocarcinoma/squamous cell carcinoma was analyzed based on TCGA data set, TIMER database and R language data package. The prognostic relationship and diagnostic value of VPS72 were evaluated with Kaplan-Meier Plotter and ROC curve online software. The interacting proteins and co-expressed genes of VPS72 were screened with STRING and LinkedOmics, and GO/KEGG functional enrichment analysis was performed with LinkedOmics. The correlation between the expression of VPS72 and immune cell infiltration was analyzed with TIMER. The correlation between VPS72 expression and different immune subtypes was analyzed in TISIDB database. Results VPS72 was highly expressed in lung adenocarcinoma/squamous cell carcinoma. Lung adenocarcinoma patients with high expression of VPS72 had significantly shorter overall survival(P=0.01), but there was no significant difference in the overall survival of lung squamous cell carcinoma patients with high expression of VPS72(P=0.17). PPI analysis showed that VPS72 interacted with 10 proteins, including H2AFZ, RUVBL1, DMAP1, and so on. GO/KEGG functional enrichment analysis showed that VPS72 was mainly involved in spliceosome and ribosome synthesis. The expression of VPS72 in lung adenocarcinoma was negatively correlated with the infiltration of a variety of immune cells, including B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils and dendritic cells. In lung squamous cell carcinoma, VPS72 expression was negatively correlated with macrophages and neutrophils. In lung adenocarcinoma/squamous cell carcinoma, VPS72 expression was correlated with 6 immune subtypes. Conclusion The expression of VPS72 is significantly increased in lung adenocarcinoma/squamous cell carcinoma, which is related to the prognosis of lung adenocarcinoma and involved in a variety of pathways and immune cells. VPS72 may become a new target for prognosis prediction and treatment of lung adenocarcinoma/squamous cell carcinoma.

Key words: Lung adenocarcinoma, Lung squamous cell carcinoma, Vacuolar protein sorting 72 homolog, The cancer genome atlas, Immune infiltration

中图分类号:

R734.2

孟健丽,王庆港. 生物信息学方法探讨VPS72在肺腺/鳞癌中的表达及潜在作用机制[J]. 山东大学学报 (医学版), 2023, 61(8): 40-49.

MENG Jianli, WANG Qinggang. Expression and potential mechanism of VPS72 in lung adenocarcinoma/ squamous cell carcinoma by integrated bioinformatics analysis[J]. Journal of Shandong University (Health Sciences), 2023, 61(8): 40-49.

参考文献

[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33.
[2] Coudray N, Ocampo PS, Sakellaropoulos T, et al. Classification and mutation prediction from non-small cell lung cancer histopathology images using deep learning[J]. Nat Med, 2018, 24(10): 1559-1567.
[3] Ren YJ, Zhao SS, Jiang DD, et al. Proteomic biomarkers for lung cancer progression[J]. Biomark Med, 2018, 12(3): 205-215.
[4] Horikawa I, Tanaka H, Yuasa Y, et al. Forced expression of YL-1 protein suppresses the anchorage-independent growth of Kirsten sarcoma virus-transformed NIH3T3 cells[J]. Exp Cell Res, 1995, 220(1): 11-17.
[5] Chen TJ, Tu YN, Lv DN, et al. Vacuolar protein sorting-associated protein 72 homolog(VPS72)binding to lysine acetyltransferase 5(KAT5)promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway[J]. Bioengineered, 2022, 13(4): 9197-9210.
[6] 刘梦媛, 郑翔, 许永杰, 等. 利用TCGA数据库研究ERGIC3在肺腺癌免疫微环境中的作用及其预后评价中的价值[J]. 遵义医科大学学报, 2022, 45(4): 450-456. LIU Mengyuan, ZHENG Xiang, XU Yongjie, et al. Prognostic value of ERGIC3 and its role on immune microenvironment in lung adenocarcinoma based on TCGA database[J]. Journal of Zunyi Medical University, 2022, 45(4): 450-456.
[7] Lánczky A, Gyorffy B. Web-based survival analysis tool tailored for medical research(KMplot): development and implementation[J]. J Med Internet Res, 2021, 23(7): e27633. doi:10.2196/27633.
[8] 尉洁, 宋娇娇, 赵晋芳, 等. 基于贝叶斯估计的诊断试验ROC曲线回归模型[J]. 中国卫生统计, 2010, 27(2): 152-154. YU Jie, SONG Jiaojiao, ZHAO Jinfang, et al. ROC regression model based on Bayesian estimation in diagnostic test[J]. Chinese Journal of Health Statistics, 2010, 27(2): 152-154.
[9] 刘腾,马迎春. 基于生物信息库病例分析ECT2在子宫内膜癌中的表达及临床意义[J]. 山东大学学报(医学版), 2022, 60(8): 63-71. LIU Teng, MA Yingchun. Expression of ECT2 in uterine corpus endometrial carcinoma and its clinical significance based on bioinformatics database[J]. Journal of Shandong University(Health Sciences), 2022, 60(8): 63-71.
[10] Vasaikar SV, Straub P, Wang J, et al. LinkedOmics: analyzing multi-omics data within and across 32 cancer types[J]. Nucleic Acids Res, 2018, 46(D1): D956-D963.
[11] Li TW, Fu JX, Zeng ZX, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells[J]. Nucleic Acids Res, 2020, 48(W1): W509-W514.
[12] Ru BB, Wong CN, Tong Y, et al. TISIDB: an integrated repository portal for tumor-immune system interactions[J]. Bioinformatics, 2019, 35(20): 4200-4202.
[13] 张同海, 王劲松, 黄文斌, 等. 联合检测TTF1、CK5/6、p63和napsinA在肺鳞癌和腺癌鉴别诊断中的价值[J]. 临床与实验病理学杂志, 2012, 28(8): 918-920. ZHANG Tonghai, WANG Jinsong, HUANG Wenbin, et al. Value of combined detection of TTF1, CK5/6, p63 and napsinA in differential diagnosis of lung squamous cell carcinoma and adenocarcinoma[J]. Chinese Journal of Clinical and Experimental Pathology, 2012, 28(8): 918-920.
[14] Moreno-Andrés D, Yokoyama H, Scheufen A, et al. VPS72/YL1-mediated H2A.Z deposition is required for nuclear reassembly after mitosis[J]. Cells, 2020, 9(7): 1702. doi:10.3390/cells9071702.
[15] Cai Y, Jin JJ, Florens L, et al. The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes[J]. J Biol Chem, 2005, 280(14): 13665-13670.
[16] Latrick CM, Marek M, Ouararhni K, et al. Molecular basis and specificity of H2A.Z-H2B recognition and deposition by the histone chaperone YL1[J]. Nat Struct Mol Biol, 2016, 23(4): 309-316.
[17] 管晓翔, 陈龙邦. 组蛋白乙酰化修饰在基因表达调控中的作用机制[J]. 中华肿瘤防治杂志, 2007, 14(4): 307-310. GUAN Xiaoxiang, CHEN Longbang. Role of histone acetylation modification in posttranscriptional gene expression[J]. Chinese Journal of Cancer Prevention and Treatment, 2007, 14(4): 307-310.
[18] Lin Y, Liang R, Qiu YF, et al. Expression and gene regulation network of RBM8A in hepatocellular carcinoma based on data mining[J]. Aging, 2019, 11(2): 423-447.
[19] 魏小勇, 黎才海, 饶荣生. p38 MAPK信号通路与肿瘤的关系[J]. 实用癌症杂志, 2009, 24(1): 101-103. WEI Xiaoyong, LI Caihai, RAO Rongsheng. Relationship between p38 MAPK signal pathway and tumor[J]. Practical Journal of Cancer, 2009, 24(1): 101-103.
[20] Fan YM, Liu B, Chen F, et al. Hepcidin upregulation in lung cancer: a potential TherapeuticTarget associated with immune infiltration[J]. Front Immunol, 2021, 12: 612144. doi:10.3389/fimmu.2021.612144.
[21] 韦燕琳, 李梅华. SIRT1基因与肺癌免疫浸润水平及临床预后分析[J]. 广西医科大学学报, 2020, 37(6): 1095-1100. WEI Yanlin, LI Meihua. Analysis of the relationship between SIRT1 gene and immune infiltration level and clinical prognosis of lung cancer[J]. Journal of Guangxi Medical University, 2020, 37(6): 1095-1100.
[22] 高维龙, 梁贵友, 郭强, 等. 预后标志物STEAP与肺腺癌免疫浸润相关[J]. 中国免疫学杂志, 2021, 37(19): 2357-2363, 2369. GAO Weilong, LIANG Guiyou, GUO Qiang, et al. Prognostic marker STEAP1 is correlated with immune infiltration of lung adenocarcinoma[J]. Chinese Journal of Immunology, 2021, 37(19): 2357-2363, 2369.
[23] Cassetta L, Pollard JW. Targeting macrophages: therapeutic approaches in cancer[J]. Nat Rev Drug Discov, 2018, 17(12): 887-904.
[24] Kargl J, Busch SE, Yang GH, et al. Neutrophils dominate the immune cell composition in non-small cell lung cancer[J]. Nat Commun, 2017, 8: 14381. doi:10.1038/ncomms14381.
[25] Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer[J]. Nat Rev Clin Oncol, 2019, 16(10): 601-620.

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