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基于生物信息学分析WDR43在肝细胞肝癌中的表达及临床价值
作者:冯时1  张宗耀1  卜旻淳1  吴小宇1  曹先东2 
单位:1. 安徽医科大学 研究生学院, 安徽 合肥 230000;
2. 安徽医科大学第一附属医院 普外科, 安徽 合肥 230000
关键词:WDR43 肝细胞肝癌 预后 数据挖掘 
分类号:R735.7
出版年·卷·期(页码):2021·49·第八期(870-876)
摘要:

目的:通过数据挖掘的方法探究WD重复蛋白43(WDR43)在肝细胞肝癌(HCC)中的表达水平,分析其与HCC预后及肿瘤免疫浸润的相关性。方法:通过检索肿瘤免疫评估(TIMER)数据库和GEPIA数据库获得WDR43在HCC组织和正常肝组织中的差异性表达,检索WDR43在Kaplan-Meier Plotter数据库的HCC预后结果,然后通过GEPIA数据库进行验证;检索Timer数据库获得WDR43与HCC组织免疫浸润水平及肿瘤相关巨噬细胞表面标志物的相关性。结果:WDR43在HCC中的表达较正常肝组织高,且随着HCC临床分期的升高,WDR43的表达存在上调趋势;WDR43高表达与HCC预后不良呈正相关([总生存率(OS):HR=1.7,P=0.002 9;无病生存率(DFS):HR=1.4,P=0.023];WDR43表达促进HCC免疫细胞(B细胞、CD4+T细胞、CD8+T细胞、中性粒细胞、巨噬细胞和树突状细胞)浸润(P<0.01);HCC中WDR43表达水平与多数免疫细胞标志物正相关且存在明显差异(P<0.001)。结论:通过多个数据库研究发现WDR43在HCC中高表达,并且与HCC的不良预后以及肿瘤相关免疫细胞浸润有关。

Objective: To explore the expression level of WD repeat protein 43(WDR43) in hepatocellular carcinoma(HCC) by data mining, and analyze its correlation with prognosis and tumor immune infiltration. Methods: The differential expression of WDR43 in HCC tissues and normal liver tissues was obtained by searching tumor immune estimation resource(TIMER) database and GEPIA database.The prognosis of WDR43 in Kaplan-Meier Plotter database was retrieved, and then verified by GEPIA database.The correlation between WDR43 and the level of HCC tissue immune infiltration and tumor-related macrophage surface markers was searched in the TIMER database. Results: The expression of WDR43 in HCC was higher than that in normal liver tissue, and with the clinical stage of HCCincreased, the expression of WDR43 had an up-regulating trend; high expression of WDR43 was positively correlated with poor prognosis of HCC(OS:HR=1.7, P=0.002 9; DFS:HR=1.4, P=0.023); WDR43 expression promoted the infiltration of HCC immune cells(B cells, CD4+T cells, CD8+T cells, neutrophils, macrophages and dendritic cells)(P<0.01); WDR43 expression level in HCC was positively correlated with most immune cell markers and there were significant differences(P<0.001). Conclusion: Through multiple database studies, it is found that WDR43 is highly expressed in HCC and is related to the poor prognosis of HCC and tumor-related immune cell infiltration.

参考文献:

[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
[2] SICA A, INVERNIZZI P, MANTOVANI A.Macrophage plasticity and polarization in liver homeostasis and pathology[J]. Hepatology, 2014, 59(5):2034-2042.
[3] LI D, ROBERTS R.WD-repeat proteins:structure characteristics, biological function, and their involvement in human diseases[J]. Cell Mol Life Sci, 2001, 58(14):2085-2097.
[4] CHACÓN S S, WANG F, THOMAS L R, et al. Discovery of WD Repeat-Containing Protein 5(WDR5)-MYC inhibitors using fragment-based methods and structure-based design[J]. J Med Chem, 2020, 63(8):4315-4333.
[5] BI X, XU Y, LI T, et al. RNA targets ribogenesis factor WDR43 to chromatin for transcription and pluripotency control[J]. Mol Cell, 2019, 75(1):102-116.e9.
[6] SIEGEL R L, MILLER K D, JEMALA.Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1):7-34.
[7] 郑声琴, 刘平, 范璟, 等.放射治疗联合免疫治疗用于肿瘤治疗的研究进展[J]. 东南大学学报(医学版), 2019, 38(6):1086-1090.
[8] SMITH T F, GAITATZES C, SAXENA K, et al. The WD repeat:a common architecture for diverse functions[J]. Trends Biochem Sci, 1999, 24(5):181-185.
[9] HENNING K A, LI L, IYER N, et al. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase Ⅱ TFIIH[J]. Cell, 1995, 82(4):555-564.
[10] HANDSCHUG K, SPERLING S, YOON S J, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene[J]. Hum Mol Genet, 2001, 10(3):283-290.
[11] MOOKHERJEE S, CHAKRABORTY S, VISHAL M, et al. WDR36 variants in East Indian primary open-angle glaucoma patients[J]. Mol Vis, 2011, 17:2618-2627.
[12] WANG C L, WANG C I, LIAO P C, et al. Discovery of retinoblastoma-associated binding protein 46 as a novel prognostic marker for distant metastasis in nonsmall cell lung cancer by combined analysis of cancer cell secretome and pleural effusion proteome[J]. J Proteome Res, 2009, 8(10):4428-4440.
[13] XU H, CHEN Y, TAN C, et al. High expression of WDR1 in primary glioblastoma is associated with poor prognosis[J]. Am J Transl Res, 2016, 8(2):1253-1264.
[14] THAKER A, RAHMAN K W, WU J, et al. Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer[J]. Mol Cancer Res, 2007, 5(2):171-181.
[15] PENA C, HURT E, PANSE V G.Eukaryotic ribosome assembly, transport and quality control[J]. Nat Struct Mol Biol, 2017, 24(9):689-699.
[16] SILVA F P, HAMAMOTO R, NAKAMURA Y, et al. WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human hepatocellular carcinoma and involved in cell proliferation[J]. Neoplasia, 2005, 7(4):348-355.
[17] ZHOU S, CAO H, ZHAO Y, et al. RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation[J]. Oncol Lett, 2016, 12(6):5303-5308.
[18] LIU X, WU S, YANG Y, et al. The prognostic landscape of tumor-infiltrating immune cell and immunomodulators in lung cancer[J]. Biomed Pharmacother, 2017, 95:55-61.

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