Abstract:Objective To screen out important genes associated with poor prognosis of ovarian cancer based on comprehensive bioinformatics analysis. Methods The expression profiles were obtained from the gene expression compilation database, and the differential expression genes (DEG) with │logFC│> 1.5 and P < 0.05 were identified from the gene expression omnibus database. Functional enrichment, protein-protein interaction (PPI) network construction, functional modules analysis, survival analysis, and correlation analysis were performed. Results Firstly, 135 uniformly expressed genes were identified, and 33 up-regulated DEG genes were mainly concentrated in mitotic spindle assembly checkpoint and chromosome separation regulation; a total of 102 DEG downregulation was mainly concentrated in the regulation of neurotransmitter level and protein serine / threonine kinase activity. Then, a PPI network was constructed, and 20 hub genes were screened for survival analysis and expression correlation analysis. At the same time, suitable modules were screened and pathway enrichment analysis was conducted for genes. Finally, the intersection of UBE2C, TTK and CP were found to be highly expressed in ovarian cancer and lead to poor prognosis. Conclusion Three key candidate genes affecting the prognosis of ovarian cancer patients are screened out through comprehensive bioinformatics analysis based on database which can provide new ideas for treatment.
马惠涵1 秘嘉庆1 秦倩1 马梅杰1 冯勤梅2▲. 基于生物信息学分析UBE2C、TTK和CP对卵巢癌预后的影响[J]. 中国医药导报, 2022, 19(4): 22-27.
MA Huihan1 MI Jiaqing1 QIN Qian1 MA Meijie1 FENG Qinmei2▲. Analysis of the effect of UBE2C, TTK and CP on prognosis of ovrian cancer based on bioinformatics#br#. 中国医药导报, 2022, 19(4): 22-27.
[1] Ferlay J,Colombet M,Soerjomataram I,et al. Cancer statistics for the year 2020:An overview [J]. Int J Cancer,2021,149(4):777-789.
[2] Swisher EM,Kaufmann SH,Birrer MJ,et al. Exploring the relationship between homologous recombination score and progression-free survival in BRCA wildtype ovarian carcinoma: Analysis of veliparib plus carboplatin/paclitaxel in the velia study [J]. Gynecologic Oncology,2020,159(S1):51.
[3] Hrdlickova R,Toloue M,Tian B. RNA-Seq methods for transcriptome analysis [J]. Wiley Interdiscip Rev RNA,2017,8(1):1-24.
[4] Leoutsakou T,Talieri M,Scorilas A. Expression analysis and prognostic significance of the SRA1 gene,in ovarian cancer [J]. Biochem Biophys Res Commun,2006,344(36):667-674.
[5] Dong Y,Li J,Han F,et al. High IGF2 expression is associated with poor clinical outcome in human ovarian cancer [J]. Oncol Rep,2015,34:936-942.
[6] Fu Z,Wang C,Chen Y,et al. Down-regulation of UTP23 promotes paclitaxel resistance and predicts poorer prognosis in ovarian cancer [J]. Pathol Res Pract,2019,36(26):152625.
[7] Mehmood A,Laiho A,Ven?覿l?覿inen MS,et al. Systematic evaluation of differential splicing tools for RNA-seq studies [J]. Brief Bioinform,2020,21(6):2052-2065.
[8] Chen H,Boutros PC. VennDiagram: A package for the generation of highly-customizable Venn and Euler diagrams in R [J]. BMC Bioinformatics,2011,12(32):35-41.
[9] Rian K,Hidalgo MR,?覶ubuk C,et al. Genome-scale mechanistic modeling of signaling pathways made easy:a Bioconductor/cytoscape/web server framework for the analysis of omic data [J]. Computat Struct Biotechnol J,2021,21(19):2968-2978.
[10] Yeung T,Leung CS,Wong K,et al. ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells [J]. Oncotarget,2017,8(10):16951-16963.
[11] Erin RK,Celestine ST,Yvonne TM,et al. The Anterior Gradient Homolog 3 (AGR3) Gene Is Associated With Differentiation and Survival in Ovarian Cancer [J]. Am J Surg Pathol,2011,35(6):904-912.
[12] Mok S,Bonome T,Vathipadiekal V,et al. A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor:microfibril-associated glycoprotein 2 [J]. Cancer Cell,2009,16(6):521-532.
[13] Vinod V,Victoria W,Wei W,et al. Creation of a Human Secretome:A Novel Composite Library of Human Secreted Proteins:Validation Using Ovarian Cancer Gene Expression Data and a Virtual Secretome Array [J]. Clin Cancer Res,2015,21(21):4960-4969.
[14] Dastsooz H,Cereda M,Donna D,et al. A Comprehensive Bioinformatics Analysis of UBE2C in Cancers [J]. Int J Mol Sci,2019,20(9):22-28.
[15] Wang R,Song Y,Liu X,et al. UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A [J]. Int J Oncol,2017,50(4):1116-1126.
[16] Yuan L,Chen L,Qian K,et al. Genomics Data Co-expression network analysis identi fi ed six hub genes in association with progression and prognosis in human clear cell renal cell carcinoma(ccRCC) [J]. Genomics Data,2017,14(36):132-140.
[17] Martínez-Canales S,Nuncia-Cantarero M,Pandiella A,et al. Functional transcriptomic annotation and protein-protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer [J]. Cancer Med,2018,7(36):1896-1907.
[18] Fang Q,Chen Xl,Zhang L,et al. The essential roles of Mps1 in spermatogenesis and fertility in mice [J]. Cell Death Dis,2021,12(6):531.
[19] Tang J,Lu M,Cui Q,et al. Overexpression of ASPM,CDC20,and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis [J]. Front Oncol,2019,9(12):1-14.
[20] Zhang XL,Han WX,Ma YM,et al. Expression of tyrosine and threonine protein kinase in carcinogenic process of colorectal cancer and its relationship with prognosis [J]. Zhonghua Zhong Liu Za Zhi[Chinese Journal of Oncology],2017,39(65):172-177.
[21] Feng H,Gu ZY,Li Q,et al. Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis [J]. J Ovarian Res,2019,12(3):1-9.
[22] Zeng DW,Dong J,Jiang JJ,et al. Ceruloplasmin,a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase [J]. World J Gastroenterol,2016,22(6):9586-9594.
[23] Arner E,Forrest ARR,Ehrlund A,et al. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells [J]. PLoS One,2014,9(32):1-5.
[24] Matsuoka R,Shiba-Ishii A,Nakano N,et al. Heterotopic production of ceruloplasmin by lung adenocarcinoma is significantly correlated with prognosis [J]. Lung Cancer,2018,118(16):97-104.
[25] Lee CM,Lo HW,Shao RP,et al. Selective Activation of Ceruloplasmin Promoter in Ovarian Tumors:Potential Use for Gene Therapy [J]. Cancer Res,2004,64(26):1788-1793.