[1]魏本飞,王 洁.基于生物信息学的宫颈癌关键基因筛选及生物学途径分析[J].医学信息,2023,36(17):7-14.[doi:10.3969/j.issn.1006-1959.2023.17.002]
 WEI Ben-fei,WANG Jie.Key Gene Screening and Biological Pathway Analysis of Cervical Cancer Based on Bioinformatics[J].Journal of Medical Information,2023,36(17):7-14.[doi:10.3969/j.issn.1006-1959.2023.17.002]
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基于生物信息学的宫颈癌关键基因筛选及生物学途径分析()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年17期
页码:
7-14
栏目:
生物信息学
出版日期:
2023-09-01

文章信息/Info

Title:
Key Gene Screening and Biological Pathway Analysis of Cervical Cancer Based on Bioinformatics
文章编号:
1006-1959(2023)17-0007-08
作者:
魏本飞王 洁
(扬州大学附属医院肿瘤科,江苏 扬州 225000)
Author(s):
WEI Ben-feiWANG Jie
(Department of Oncology,Affiliated Hospital of Yangzhou University,Yangzhou 225000,Jiangsu,China)
关键词:
宫颈癌差异表达基因分子标志物
Keywords:
Cervical cancerDifferentially expressed genesMolecular markers
分类号:
R737.33
DOI:
10.3969/j.issn.1006-1959.2023.17.002
文献标志码:
A
摘要:
目的 用生物信息学技术分析宫颈癌发生、发展的关键基因及生物学途径,为宫颈癌的临床诊断、预后评估及靶向治疗提供理论依据。方法 在NCBI-GEO数据库中下载GSE6791、GSE63514、GSE7803、GSE52903和GSE9750共5组宫颈癌基因芯片表达谱,利用Venn在线软件对数据进行整合分析得到宫颈癌组织和正常宫颈组织的差异表达基因(DEGs),并对差异表达基因进行GO、KEGG富集分析。利用STRING数据库构建DEGs的蛋白互作网络,基于Cytoscape软件的MCODE插件识别重要的功能模块,基于cytoHubba插件筛选出关键基因,并通过GEPIA数据库对关键基因进行验证。结果 共筛选出138个DEGs,其中上调基因81个,下调基因57个。GO功能分析显示,DEGs涉及的分子功能包括蛋白质结合、DNA复制起点结合、染色质结合、丝氨酸型肽酶及内肽酶活性、蛋白激酶结合、DNA解旋酶活性、ATP结合。KEGG通路分析显示,DEGs主要富集在细胞周期、DNA复制、卵母细胞减数分裂、p53信号通路、膀胱癌等通路。通过蛋白互作网络发现3个重要功能模块,筛选出16个关键基因,其中与患者预后相关基因有3个:CDC45、TOP2A、RRM2。结论 TOP2A、CDC45、RRM2在宫颈癌组织中高表达,与患者预后明显相关,是宫颈癌临床诊断、治疗及预后的潜在分子标志物和作用靶点。
Abstract:
Objective To analyze the key genes and biological pathways of the occurrence and development of cervical cancer by bioinformatics, and to provide theoretical basis for clinical diagnosis, prognosis evaluation and targeted therapy of cervical cancer.Methods Five groups of cervical cancer gene chip expression profiles of GSE6791, GSE63514, GSE7803, GSE52903 and GSE9750 were downloaded from NCBI-GEO database. Venn online software was used to integrate and analyze the data to obtain differentially expressed genes (DEGs) in cervical cancer tissues and normal cervical tissues, and GO and KEGG enrichment analysis were performed on differentially expressed genes. The protein interaction network of DEGs was constructed using the STRING database. The important functional modules were identified based on the MCODE plug-in of Cytoscape software. The key genes were screened based on the cytoHubba plug-in, and the key genes were verified by the GEPIA database.Results A total of 138 DEGs were screened, including 81 up-regulated genes and 57 down-regulated genes. GO functional analysis showed that the molecular functions involved in DEGs included protein binding, DNA replication origin binding, chromatin binding, serine peptidase and endopeptidase activity, protein kinase binding, DNA helicase activity, ATP binding. KEGG pathway analysis showed that DEGs were mainly enriched in cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway, bladder cancer and other pathways. Through the protein interaction network, three important functional modules were found, and 16 key genes were screened. Among them, there were three genes related to the prognosis of patients: CDC45, TOP2 A, and RRM2.Conclusion TOP2A, CDC45 and RRM2 are highly expressed in cervical cancer, which are significantly related to the prognosis of patients, and may be potential molecular markers and targets for clinical diagnosis, treatment and prognosis.

参考文献/References:

[1]Small W,Bacon MA,Bajaj A,et al.Cervical cancer:a global health crisis[J].Cancer,2017,123(13):2404-2412.[2]Siegel R,Ma JM,Zou ZH,et al.Cancer statistics,2014[J].CA A Cancer J Clin,2014,64(1):9-29.[3]Kim H,Cho WK,Kim YJ,et al.Significance of the number of high-risk factors in patients with cervical cancer treated with radical hysterectomy and concurrent chemoradiotherapy[J].Gynecol Oncol,2020,157(2):423-428.[4]Stumbar SE,Stevens M,Feld Z.Cervical cancer and its precursors: a preventative approach to screening, diagnosis, and management[J].Prim Care,2019,46(1):117-134.[5]Yao XJ,Zhang HW,Tang SJ,et al.Bioinformatics analysis to reveal potential differentially expressed long non-coding RNAs and genes associated with tumour metastasis in lung adenocarcinoma[J].Oncotargets Ther,2020,13:3197-3207.[6]Gong BJ,Kao YL,Zhang CL,et al.Identification of hub genes related to carcinogenesis and prognosis in colorectal cancer based on integrated bioinformatics[J].Mediators Inflamm,2020,2020:5934821.[7]Pyeon D,Newton MA,Lambert PF,et al.Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers[J].Cancer Res,2007,67(10):4605-4619.[8]den Boon JA,Pyeon D,Wang SS,et al.Molecular transitions from papillomavirus infection to cervical precancer and cancer: role of stromal estrogen receptor signaling[J].Proc Natl Acad Sci U S A,2015,112(25):E3255-E3264.[9]Zhai YL,Kuick R,Nan B,et al.Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion[J].Cancer Res,2007,67(21):10163-10172.[10]Medina-Martinez I,Barrón V,Roman-Bassaure E,et al.Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study[J].PLoS One,2014,9(5):e97842.[11]Scotto L,Narayan G,Nandula SV,et al.Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression[J].Genes Chromosomes Cancer,2008,47(9):755-765.[12]Vormittag-Nocito E,Groth JV,Mohapatra G.Next generation sequencing of cervical high grade dysplasia and invasive squamous cell carcinoma: a case study[J].Pathol Res Pract,2020,216(4):152863.[13]Cancer Genome Atlas Research Network,Analysis Working Group:Asan University,BC Cancer Agency,et al.Integrated genomic characterization of oesophageal carcinoma[J].Nature,2017,541(7636):169-175.[14]Wang L,Zhao HY,Xu YQ,et al.Systematic identification of lincRNA-based prognostic biomarkers by integrating lincRNA expression and copy number variation in lung adenocarcinoma[J].Int J Cancer,2019,144(7):1723-1734.[15]Szambowska A,Tessmer I,Prus P,et al.Cdc45-induced loading of human RPA onto single-stranded DNA[J].Nucleic Acids Res,2017,45(6):3217-3230.[16]Pellegrini L.Structural insights into Cdc45 function: was there a nuclease at the heart of the ancestral replisome? [J].Biophys Chem,2017,225:10-14.[17]Ke Y,Guo W,Huang S,et al.RYBP inhibits esophageal squamous cell carcinoma proliferation through downregulating CDC6 and CDC45 in G1-S phase transition process[J].Life Sci,2020,250:117578.[18]Yang SS,Ren XL,Liang YS,et al.KNK437 restricts the growth and metastasis of colorectal cancer via targeting DNAJA1/CDC45 axis[J].Oncogene,2020,39(2):249-261.[19]Yu X,Davenport JW,Urtishak KA,et al.Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci[J].Genome Res,2017,27(7):1238-1249.[20]Kou F,Sun HF,Wu L,et al.TOP2A promotes lung adenocarcinoma cells’ malignant progression and predicts poor prognosis in lung adenocarcinoma[J].J Cancer,2020,11(9):2496-2508.[21]Wang B,Shen YP,Zou Y,et al.TOP2A promotes cell migration, invasion and epithelial-mesenchymal transition in cervical cancer via activating the PI3K/AKT signaling[J].Cancer Manag Res,2020,12:3807-3814.[22]Shao J,Liu X,Zhu L,et al.Targeting ribonucleotide reductase for cancer therapy[J].Expert Opin Ther Targets,2013,17(12):1423-1437.[23]Chen CW,Li YM,Hu SY,et al.DHS (trans-4, 4’-dihydroxystilbene) suppresses DNA replication and tumor growth by inhibiting RRM2 (ribonucleotide reductase regulatory subunit M2)[J].Oncogene,2019,38(13):2364-2379.[24]Li C,Zheng JF,Chen S,et al.RRM2 promotes the progression of human glioblastoma[J].J Cell Physiol,2018,233(10):6759-6767.[25]Zhang S,Yan L,Cui C,et al.Downregulation of RRM2 attenuates retroperitoneal liposarcoma progression via the Akt/mTOR/4EBP1 pathway: clinical, biological, and therapeutic significance[J].Oncotargets Ther,2020,13:6523-6537.[26]Grolmusz VK,Karászi K,Micsik T,et al.Cell cycle dependent RRM2 may serve as proliferation marker and pharmaceutical target in adrenocortical cancer[J].Am J Cancer Res,2016,6(9):2041-2053.

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更新日期/Last Update: 1900-01-01