基于生物信息学鉴定CCNB2为肾嫌色细胞癌进展的关键基因
Bioinformatics-Based Identification of CCNB2 as a Key Gene in the Progression of Chromophobe Renal Cell Carcinoma
DOI: 10.12677/acm.2024.143886, PDF,    科研立项经费支持
作者: 谢义腾*, 张元峰, 张荣贵#：重庆医科大学附属第二医院泌尿外科，重庆
关键词: 嫌色细胞癌；生物信息学分析；CCNB2；GSE15641；chrcc； Bioinformatics Analysis； CCNB2； GSE15641
摘要: 本研究旨在通过生物信息学方法筛选与肾嫌色细胞癌(Chromophobe renal cell carcinoma, chrcc)相关的生物标志物，作为预测chrcc预后的关键基因。GSE15641数据集从Gene Expression Omnibus (GEO)数据库中获取，共鉴定出1153个差异表达基因(DEGs)。随后，检测差异表达基因进行基因本体(GO)注释和京都基因基因组百科全书(KEGG)途径富集分析。此外，利用Cytoscape软件构建蛋白–蛋白相互作用(PPI)网络并可视化鉴定关键基因，包括KRAS、EGFR、EHHADH和CCNB2，根据Kaplan-Meier (K-M)生存分析，CCNB2是唯一重要的核心基因。根据我们的研究结果，CCNB2在The Cancer Genome Atlas(TCGA)-chrcc患者中的表达明显高于正常样本，并且CCNB2在癌症组织中的高表达与不良的临床病理因素有关。CCNB2高表达组与低表达组相比，总生存期(OS)和无进展间期(PFI)明显较差。同时，免疫浸润分析显示CCNB2表达与chrcc患者Th2细胞富集水平呈正相关，CCNB2表达与细胞毒性细胞和DC细胞呈负相关。最后，根据包括CCNB2基因在内的基因集富集分析(Gene Set Enrichment Analysis, GSEA)富集结果，肝癌(HCC)亚类与乳腺癌(BC)的分类存在显著差异。在目前的工作中，CCNB2可以被认为是chrcc的预测性分子标记物和潜在的治疗靶点。
Abstract: The present work aimed to screen biomarkers associated with chromophobe renal cell carcinoma (chrcc) by bioinformatics methods as key genes to predict the prognosis of chrcc. The GSE15641 dataset was acquired from Gene Expression Omnibus (GEO) database, and totally of 1153 differentially expressed genes (DEGs) were identified. Thereafter, DEGs were detected to carry out Gene Ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis. Moreover, the protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape software to identify pivotal genes, including KRAS, EGFR, EHHADH and CCNB2, with CCNB2 being identified as the only significant core gene according to Kaplan-Meier (K-M) survival analysis. According to our results, CCNB2 expression was notably higher in The Cancer Genome Atlas (TCGA)-chrcc patients than in normal samples, and the high CCNB2 expression in cancer tissues was associated with adverse clinicopathological factors. The high CCNB2 expression group had markedly poor overall survival (OS) and progression-free interval (PFI) compared with low expression group. Meanwhile, immune infiltration analysis demonstrated a positive correlation between CCNB2 expression and Th2 cells enrichment levels in chrcc patients, and a negative correlation between CCNB2 expression and Cytotoxic cells as well as DC cells. At last, according to the Gene Set Enrichment Analysis (GSEA) enrichment results including CCNB2 gene, there was a significant difference in the classification of hepatocellular carcinoma (HCC) subclass and breast cancer (BC). In the current work, CCNB2 can be considered as a predictive molecular marker and a potential therapeutic target for chrcc.
文章引用：谢义腾, 张元峰, 张荣贵. 基于生物信息学鉴定CCNB2为肾嫌色细胞癌进展的关键基因[J]. 临床医学进展, 2024, 14(3): 1620-1631. https://doi.org/10.12677/acm.2024.143886

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] Ljungberg, B., Albiges, L., Abu-Ghanem, Y., Bedke, J., Capitanio, U., et al. (2022) European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. European Urology, 82, 399-410. [Google Scholar] [CrossRef] [PubMed]
[3] Garje, R., Elhag, D., Yasin, H.A., Acharya, L., Vaena, D. and Dahmoush, L. (2021) Comprehensive Review of Chromophobe Renal Cell Carcinoma. Critical Reviews in Oncology/Hematology, 160, 103287. [Google Scholar] [CrossRef] [PubMed]
[4] Capitanio, U. and Montorsi, F. (2016) Renal Cancer. Lancet, 387, 894-906. [Google Scholar] [CrossRef] 
[5] 王伟玲, 吕明晓, 吉敬. 细胞周期调控蛋白作为抗肿瘤药物潜在靶标的研究进展[C]//南京康复医学会. 第二届全国康复与临床药学学术交流会议论文集(四). 2022: 400-404.[CrossRef] 
[6] Malumbres, M. and Barbacid, M. (2005) Mammalian Cyclin-Dependent Kinases. Trends in Biochemical Sciences, 30, 630-641. [Google Scholar] [CrossRef] [PubMed]
[7] Qian, D., Zheng, W., Chen, C., Jing, G. and Huang, J. (2020) Roles of CCNB2 and NKX3-1 in Nasopharyngeal Carcinoma. Cancer Biotherapy and Radiopharmaceuticals, 35, 208-213. [Google Scholar] [CrossRef] [PubMed]
[8] Hoffmann, T.K., Trellakis, S., Okulicz, K., Schuler, P., Greve, J., Arnolds, J., et al. (2011) Cyclin B1 Expression and P53 Status in Squamous Cell Carcinomas of the Head and Neck. Anticancer Research, 31, 3151-3157.
[9] Niemira, M., Collin, F., Szalkowska, A., Bielska, A., Chwialkowska, K., Reszec, J., Niklinski, J., Kwasniewski, M. and Kretowski, A. (2019) Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA). Cancers (Basel), 12, 37. [Google Scholar] [CrossRef] [PubMed]
[10] Aljohani, A.I., Toss, M.S., El-Sharawy, K.A., Mirza, S., Ball, G.R., Green, A.R., Rakha, E.A. (2022) Upregulation of Cyclin B2 (CCNB2) in Breast Cancer Contributes to the Development of Lymphovascular Invasion. American Journal of Cancer Research, 12, 469-489.
[11] Yang, D., He, Y., Wu, B., Deng, Y., Wang, N., Li, M. and Liu, Y. (2020) Integrated Bioinformatics Analysis for the Screening of Hub Genes and Therapeutic Drugs in Ovarian Cancer. Journal of Ovarian Research, 13, Article No. 10. [Google Scholar] [CrossRef] [PubMed]
[12] Yin, S., Yang, S., Luo, Y., Lu, J., Hu, G., Wang, K., Shao, Y., Zhou, S., Koo, S., Qiu, Y., Wang, T. and Yu, H. (2021) Cyclin-Dependent Kinase 1 as a Potential Target for Lycorine against Hepatocellular Carcinoma. Biochemical Pharmacology, 193, 114806. [Google Scholar] [CrossRef] [PubMed]
[13] Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S. and Zhou, H. (2021) Signaling Pathways in Cancer-Associated Fibroblasts and Targeted Therapy for Cancer. Signal Transduction and Targeted Therapy, 6, Article No. 218. [Google Scholar] [CrossRef] [PubMed]
[14] Reina-Campos, M., Moscat, J. and Diaz-Meco, M. (2017) Metabolism Shapes the Tumor Microenvironment. Current Opinion in Cell Biology, 48, 47-53. [Google Scholar] [CrossRef] [PubMed]
[15] Gajewski, T.F., Schreiber, H. and Fu, Y.X. (2013) Innate and Adaptive Immune Cells in the Tumor Microenvironment. Nature Immunology, 14, 1014-1022. [Google Scholar] [CrossRef] [PubMed]
[16] Zou, Y., Ruan, S., Jin, L., Chen, Z., Han, H., Zhang, Y., Jian, Z., Lin, Y., Shi, N. and Jin, H. (2020) CDK1, CCNB1, and CCNB2 Are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma. Medical Science Monitor, 26, E925289. [Google Scholar] [CrossRef] 
[17] Maier, E., Duschl, A. and Horejs-Hoeck, J. (2012) STAT6-Dependent and-Independent Mechanisms in Th2 Polarization. European Journal of Immunology, 42, 2827-2833. [Google Scholar] [CrossRef] [PubMed]
[18] Mantovani, A., Allavena, P., Sica, A. and Balkwill, F. (2008) Cancer-Related Inflammation. Nature, 454, 436-444. [Google Scholar] [CrossRef] [PubMed]
[19] Lee, H.L., Jang, J.W., Lee, S.W., Yoo, S.H., Kwon, J.H., Nam, S.W., Bae, S.H., Choi, J.Y., Han, N.I. and Yoon, S.K. (2019) Inflammatory Cytokines and Change of Th1/Th2 Balance as Prognostic Indicators for Hepatocellular Carcinoma in Patients Treated with Transarterial Chemoembolization. Scientific Reports, 9, Article No. 3260. [Google Scholar] [CrossRef] [PubMed]
[20] Budhu, A., Forgues, M., Ye, Q.H., Jia, H.L., He, P., Zanetti, K.A., et al. (2006) Prediction of Venous Metastases, Recurrence, and Prognosis in Hepatocellular Carcinoma Based on a Unique Immune Response Signature of the Liver Microenvironment. Cancer Cell, 10, 99-111. [Google Scholar] [CrossRef] [PubMed]
[21] Oh, D.Y. and Fong, L. (2021) Cytotoxic CD4 T Cells in Cancer: Expanding the Immune Effector Toolbox. Immunity, 54, 2701-2711. [Google Scholar] [CrossRef] [PubMed]
[22] Wculek, S.K., Cueto, F.J., Mujal, A.M., Melero, I., Krummel, M.F. and Sancho, D. (2020) Dendritic Cells in Cancer Immunology and Immunotherapy. Nature Reviews Immunology, 20, 7-24. [Google Scholar] [CrossRef] [PubMed]
[23] Xiao, Y., Ma, J., Guo, C., Liu, D., Pan, J. and Huang, X. (2022) Cyclin B2 Overexpression Promotes Tumour Growth by Regulating Jagged 1 in Hepatocellular Carcinoma. Aging, 14, 2855-2867. [Google Scholar] [CrossRef] [PubMed]

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