肾透明细胞癌核心基因的生物信息学分析及<i>AURKB</i>表达的验证

李俊; 陶润; 王伟杰; 张家俊

doi:10.16766/j.cnki.issn.1674-4152.003049

肾透明细胞癌核心基因的生物信息学分析及AURKB表达的验证

doi: 10.16766/j.cnki.issn.1674-4152.003049

蚌埠医学院第一附属医院泌尿外科，安徽蚌埠 233004

基金项目:

安徽省高校自然科学研究重点项目 KJ2020A1290

详细信息

通讯作者:
张家俊，E-mail: zsyf777@126.com

中图分类号: R737.11 R730.4
计量
- 文章访问数: 146
- HTML全文浏览量: 47
- PDF下载量: 7
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-09
- 网络出版日期: 2023-08-26

Analyze the core gene of renal clear cell carcinoma based on bioinformatics and verify the expression of AURKB

Department of Urology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的利用生物信息学手段，在肾透明细胞癌(KIRC)中筛选目标基因AURKB，分析其在肾透明细胞癌中的临床意义。方法在GEO数据库下载GSE66271数据集后，筛选差异基因。基于STRING数据库和Cytoscape软件挑选hub基因。利用GEPIA在线数据库验证基因AURKB在肾透明细胞癌组织中的表达及预后关系。通过免疫组化实验验证AURKB在肾透明细胞癌组织与癌旁正常组织的表达差异。结果对数据集GSE66271分析后，共获得517个差异基因，其中155个上调基因，362个下调基因。在差异基因网络中的10个枢纽基因，从中选取基因AURKB进行验证。GEPIA数据库分析显示AURKB高表达均显著降低了KIRC患者的总生存期(OS)及无病生存期(DFS)(均P＜0.001)，表示其可能为KIRC的促癌基因。此外AURKB的表达与KIRC患者的不同疾病阶段呈正相关关系(P＜0.001)。免疫组化实验表明AURKB蛋白表达主要在细胞核内，在癌组织中阳性表达(58.00%，29/50)高于癌旁正常组织(24.00%，12/50)，差异有统计学意义(χ²=11.947，P=0.001)。结论基因AURKB在肾透明细胞癌中高表达并导致了不良预后，证明其可能为KIRC的一个促癌基因，有望成为KIRC的治疗新靶点。
- 生物信息学分析 /
- 肾透明细胞癌 /
- 核心基因 /
- AURKB基因
Abstract: Objective The target gene AURKB was screened in renal clear cell carcinoma by bioinformatics method, and its clinical significance in renal clear cell carcinoma was analyzed. Methods The GSE66271 dataset was downloaded from GEO database and the differential genes were screened. Hub genes were selected based on STRING database and Cytoscape software. The expression and prognostic relationship of AURKB gene in renal clear cell carcinoma were verified by GEPIA online database. The difference of AURKB expression in clear cell carcinoma and adjacent normal tissue was verified by immunohistochemistry. Results A total of 517 differential genes were obtained after analysis of GSE66271 data set, including 155 up-regulated genes and 362 down-regulated genes. AURKB was selected from 10 hub genes in the differential gene network for verification. GEPIA database analysis showed that AURKB high expression significantly reduced the overall survival (OS) and disease-free survival (DFS) in KIRC patients (P < 0.05), indicating that AURKB may be a KIRC oncogenic gene. In addition, AURKB expression was positively correlated with different disease stages in KIRC patients (P < 0.05). Immunohistochemical test showed that AURKB protein was mainly expressed in the nucleus, and the positive expression in cancer tissues (58.00%, 29/50) was higher than that in adjacent normal tissues (24.00%, 12/50), the difference was statistically significant (χ²=11.947, P=0.001). Conclusion AURKB is highly expressed in renal clear cell carcinoma and leads to poor prognosis, suggesting that AURKB may be an oncogenic genes for KIRC, and is expected to be a new therapeutic target for KIRC.
- Bioinformatics analysis /
- Kidney renal clear cell carcinoma /
- Hub gene /
- AURKB gene

HTML全文

图 1 差异基因的功能富集分析及蛋白互作网络图

注：A为GO富集部分结果；B为KEGG富集的前10条通路；C为蛋白互作网络图。

Figure 1. Functional enrichment analysis of differential genes and protein interaction network diagram

下载: 全尺寸图片幻灯片

图 2 基于GEPIA数据库对AURKB的验证

注：图 2A为基因AURKB在癌组织与正常组织的表达；图 2B、3C为AURKB的表达对OS、DFS的影响；图 2D为AURKB在不同分期中的表达。

Figure 2. Verification of AURKB based on the GEPIA database

下载: 全尺寸图片幻灯片

参考文献(23)

[1]	高五岳, 郭园园, 刘贝贝, 等. 不同距离癌旁组织PD-1和PD-L1表达对肾部分切除术边距选择的临床意义[J]. 中华全科医学, 2019, 17(12): 2004-2007, 2034. doi: 10.16766/j.cnki.issn.1674-4152.001113 GAO W Y, GUO Y Y, LIU B B, et al. The clinical significances of PD-1 and PD-L1 expressions in different distant tumor adjacent tissues for selecting safe surgical margins in partial nephrectomy[J]. Chinese Journal of General Practice, 2019, 17(12): 2004-2007, 2034. doi: 10.16766/j.cnki.issn.1674-4152.001113
[2]	DI FRANCO G, PALMERI M, SBRANA A, et al. Renal cell carcinoma: the role of radical surgery on different patterns of local or distant recurrence[J]. Surg Oncol, 2020, 35: 106-113. doi: 10.1016/j.suronc.2020.08.002
[3]	SUN Z L, TAO W, GUO X D, et al. Construction of a lactate-related prognostic signature for predicting prognosis, tumor microenvironment, and immune response in kidney renal clear cell carcinoma[J]. Front Immunol, 2022, 13: 818984. DOI: 10.3389/fimmu.2022.818984.
[4]	LU M Q, XIAO L X, XU B, et al. Identification of novel genes and associated drugs in advanced clear cell renal cell carcinoma by bioinformatic methods[J]. Tohoku J Exp Med, 2022, 258(2): 79-90. doi: 10.1620/tjem.2022.J059
[5]	GLASER Z A, LOVE H D, GUO S H, et al. TPX2 as a prognostic indicator and potential therapeutic target in clear cell renal cell carcinoma[J]. Urol Oncol, 2017, 35(5): 286-293. doi: 10.1016/j.urolonc.2016.12.012
[6]	ZHANG H P, ZOU J, YIN Y, et al. Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma[J]. Peer J, 2019, 7: e8096. DOI: 10.7717/peerj.8096.
[7]	BORAH N A, REDDY M M. Aurora kinase b inhibition: a potential therapeutic strategy for cancer[J]. Molecules, 2021, 26(7): 1981. DOI: 10.3390/molecules26071981.
[8]	ALAFATE W, ZUO J, DENG Z, et al. Combined elevation of AURKB and UBE2C predicts severe outcomes and therapy resistance in glioma[J]. Pathol Res Pract, 2019, 215(10): 152557. DOI: 10.1016/j.prp.2019.152557.
[9]	BORAH N A, SRADHANJALI S, BARIK M R, et al. Aurora kinase b expression, its regulation and therapeutic targeting in human retinoblastoma[J]. Investig Ophthalmol Vis Sci, 2021, 62(3): 16. doi: 10.1167/iovs.62.3.16
[10]	WANG L S, XIAO X L, DU H. The regulation of let-7c-5p on the biological characteristics of lung adenocarcinoma cells by targeting AURKB[J]. Mol Biotechnol, 2022, 64(5): 526-534. doi: 10.1007/s12033-021-00446-0
[11]	KIM T, GARTNER A. BUB1 kinase in the regulation of mitosis[J]. Anim Cells Syst (Seoul), 2021, 25(1): 1-10. doi: 10.1080/19768354.2021.1884599
[12]	PIAO X M, YOU C, BYUN Y J, et al. Prognostic value of BUB1 for predicting non-muscle-invasive bladder cancer progression[J]. Int J Mol Sci, 2021, 22(23): 12756. DOI: 10.3390/ijms222312756.
[13]	QI W B, BAI Y P, WANG Y R, et al. BUB1 predicts poor prognosis and immune status in liver hepatocellular carcinoma[J]. APMIS, 2022, 130(7): 371-382. doi: 10.1111/apm.13219
[14]	WANG S N, LIU X Y, YANG M, et al. BUBs are new biomarkers of promoting tumorigenesis and affecting prognosis in breast cancer[J]. Dis Markers, 2022, 2022: 2760432. DOI: 10.1155/2022/2760432.
[15]	SMERTENKO A, CLARE S J, EFFERTZ K, et al. A guide to plant TPX2-like and wave-dampened2-like proteins[J]. J Exp Bot, 2021, 72(4): 1034-1045. doi: 10.1093/jxb/eraa513
[16]	YANG W N, WAN H T, SHAN R F, et al. The clinical significance and prognostic value of Xenopus kinesin-like protein 2 expressions in human tumors: a systematic review and meta-analysis[J]. J Cell Physiol, 2019, 234(9): 14991-14998. doi: 10.1002/jcp.28343
[17]	CHENG L, HUANG Y Z, CHEN W X, et al. Cell division cycle proteinising prognostic biomarker of breast cancer[J]. Biosci Rep, 2020, 40(5): BSR20191227. DOI: 10.1042/BSR20191227.
[18]	LI F, SU M Q, ZHAO H F, et al. HnRNP-F promotes cell proliferation by regulating TPX2 in bladder cancer[J]. Am J Transl Res, 2019, 11(11): 7035-7048.
[19]	赵伟杰. 基于生物信息学对肾透明细胞癌预后相关枢纽基因的探索[D]. 大连: 大连医科大学, 2022. ZHAO W J. Exploration of key genes related to prognosis of renal clear cell carcinoma based on bioinformatics[D]. Dalian : Dalian Medical University, 2022.
[20]	USTINOV N B, KORSHUNOVA A V, GUDIMCHUK N B. Protein complex NDC80: properties, functions, and possible role in pathophysiology of cell division[J]. Biochemistry (Mosc), 2020, 85(4): 448-462. doi: 10.1134/S0006297920040057
[21]	CHEN J X, ÜNALÇ E. Meiotic regulation of the NDC80 complex composition and function[J]. Curr Genet, 2021, 67(4): 511-518. doi: 10.1007/s00294-021-01174-3
[22]	CHEN X W, LI W W, XIAO L S, et al. Nuclear division cycle 80 complex is associated with malignancy and predicts poor survival of hepatocellular carcinoma[J]. Int J Clin Exp Pathol, 2019, 12(4): 1233-1247.
[23]	SUN Z Y, WANG W, GAO H, et al. Potential therapeutic targets of the nuclear division cycle 80 (NDC80) complexes genes in lung adenocarcinoma[J]. J Cancer, 2020, 11(10): 2921-2934. doi: 10.7150/jca.41834