Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (10): 99-109.doi: 10.6040/j.issn.1671-7554.0.2022.0265

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Genes associated with cervical cancer by integrated bioinformatics analysis

XIU Dejian1,2, GAO Zhengwen3, SONG Tingting4, CUI Nan5, CUI Jing6, SUN Jianping6   

  1. 1. School of Public Health, Qingdao University, Qingdao 266000, Shandong, China;
    2. Laoshan Municipal Center for Disease Control and Prevention, Qingdao 266100, Shandong, China;
    3. Anesthesiology Department, Guzhen Orthopedic Hospital of Chengyang, Qingdao 266000, Shandong, China;
    4. Quality Control Department, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao 266000, Shandong, China;
    5. Hospital Management Institute, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China;
    6. Qingdao Municipal Center for Disease Control and Prevention, Qingdao Institute of Preventive Medicine, Qingdao 266033, Shandong, China
  • Published:2022-09-30

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Abstract: Objective To identify the key genes associated with cervical cancer in TCGA and GEO databases, and to explore the molecular mechanism and clinical values. Methods Gene expression profiles of cervical cancer were obtained from TCGA and GEO databases. The differentially expressed genes(DEGs)of cervical cancer were screened with weighted gene co-expression network analysis(WGCNA). Enrich analysis and protein-protein interaction(PPI)network were performed and hub genes were identified. The associations between hub genes and prognosis, and immune cell infiltration were analyzed. Results A total of 88 DEGs were screened out. GO analysis showed that most DEGs were enriched in nuclear chromosome segregation, meiotic nuclear division, condensed chromosome and nuclear chromosome. KEGG pathway analysis showed that those DEGs were enriched in cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway and homologous recombination. A total of 20 hub genes were identified. The lower expression of mitotic arrest deficient 2 like 1(MAD2L1)was associated with longer overall survival(OS)(P=0.013). The lower expression of MAD2L1 was not associated with disease-free survival(DFS)(P>0.05). The protein level of MAD2L1 was up-regulated in cervical cancer. TIMER analysis showed that the level of MAD2L1 was significantly associated with tumor-infiltrating immune cells(P<0.05). Conclusion The candidate gene MAD2L1 associated with cervical cancer was identified, which was associated with the prognosis and immune cell infiltration of patients with cervical cancer, and may become a new target for prognosis and treatment of cervical cancer.

Key words: Cervical cancer, Differentially expressed genes, Weighted gene co-expression network analysis, Enrichment analysis, Protein-protein interaction, Biomarkers

CLC Number: 

  • R737.3
[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] Gaffney DK, Hashibe M, Kepka D, et al. Too many women are dying from cervix cancer: problems and solutions[J]. Gynecol Oncol, 2018, 151(3): 547-554.
[3] Castle PE, Einstein MH, Sahasrabuddhe VV. Cervical cancer prevention and control in women living with human immunodeficiency virus[J]. CA Cancer J Clin, 2021, 71(6): 505-526.
[4] Cohen PA, Jhingran A, Oaknin A, et al. Cervical cancer[J]. Lancet, 2019, 393(10167): 169-182.
[5] Olusola P, Banerjee HN, Philley JV, et al. Human papilloma virus-associated cervical cancer and health disparities[J]. Cells, 2019, 8(6): 622.
[6] Asthana S, Busa V, Labani S. Oral contraceptives use and risk of cervical cancer-a systematic review & meta-analysis[J]. Eur J Obstet Gynecol Reprod Biol, 2020, 247: 163-175. doi: 10.1016/j.ejogrb.2020.02.014.
[7] 赵庆庆, 尹格平. TNF-α启动子5个位点的基因多态性与山东省汉族妇女宫颈癌遗传易感性的相关性[J]. 山东大学学报(医学版), 2018, 56(2): 28-33. ZHAO Qingqing, YIN Geping. Association between genetic polymorphisms of 5 genetic loci of TNF-α promoter and genetic susceptibility to cervical cancer[J]. Journal of Shandong University(Health Sciences), 2018, 56(2): 28-33.
[8] Liontos M, Kyriazoglou A, Dimitriadis I, et al. Systemic therapy in cervical cancer: 30 years in review[J]. Crit Rev Oncol Hematol, 2019, 137: 9-17. doi: 10.1016/j.critrevonc.2019.02.009.
[9] Feng CH, Mell LK, Sharabi AB, et al. Immunotherapy with radiotherapy and chemoradiotherapy for cervical cancer[J]. Semin Radiat Oncol, 2020, 30(4): 273-280
[10] 杨佳欣, 沈铿, 王遥. 妇科恶性肿瘤保留生育功能治疗的现状与展望[J]. 山东大学学报(医学版), 2018, 56(5): 1-7. YANG Jiaxin, SHEN Keng, WANG Yao. Status and prospect of fertility preservation treatment for gynecologic malignancies[J]. Journal of Shandong University(Health Sciences), 2018, 56(5): 1-7.
[11] Mauricio D, Zeybek B, Tymon-Rosario J, et al. Immunotherapy in cervical cancer[J]. Curr Oncol Rep, 2021, 23(6): 61.
[12] Wright JD, Matsuo K, Huang Y, et al. Prognostic performance of the 2018 international federation of gynecology and obstetrics cervical cancer staging guidelines[J]. Obstet Gynecol, 2019, 134(1): 49-57.
[13] Aalijahan H, Ghorbian S. Long non-coding RNAs and cervical cancer[J]. Exp Mol Pathol, 2019, 106: 7-16. doi: 10.1016/j.yexmp.2018.11.010.
[14] Wu X, Peng L, Zhang Y, et al. Identification of key genes and pathways in cervical cancer by bioinformatics analysis[J]. Int J Med Sci, 2019, 16(6): 800-812.
[15] Yang HJ, Xue JM, Li J, et al. Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis[J]. Mol Genet Genomic Med, 2020, 8(6): e1200.
[16] Wu K, Yi Y, Liu F, et al. Identification of key pathways and genes in the progression of cervical cancer using bioinformatics analysis[J]. Oncol Lett, 2018, 16(1): 1003-1009.
[17] 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.
[18] Tang X, Xu Y, Lu L, et al. Identification of key candidate genes and small molecule drugs in cervical cancer by bioinformatics strategy[J]. Cancer Manag Res, 2018, 10: 3533-3549. doi: 10.2147/CMAR.S171661.
[19] Long NP, Jung KH, Yoon SJ, et al. Systematic assessment of cervical cancer initiation and progression uncovers genetic panels for deep learning-based early diagnosis and proposes novel diagnostic and prognostic biomarkers[J]. Oncotarget, 2017, 8(65): 109436-109456.
[20] Peng X, Zhang Y, Gao J, et al. MiR-1258 promotes the apoptosis of cervical cancer cells by regulating the E2F1/P53 signaling pathway[J]. Exp Mol Pathol, 2020, 114: 104368. doi:10.1016/j.yexmp.2020.104368.
[21] Wei W, Liu C. Prognostic and predictive roles of microRNA411 and its target STK17A in evaluating radiotherapy efficacy and their effects on cell migration and invasion via the p53 signaling pathway in cervical cancer[J]. Mol Med Rep, 2020, 21(1): 267-281.
[22] Yang WX, Pan YY, You CG. CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 may be potential therapeutic targets for hepatocellular carcinoma using integrated bioinformatic analysis[J]. Biomed Res Int, 2019, 2019: 1245072. doi: 10.1155/2019/1245072.
[23] Wang Y, Wang F, He J, et al. miR-30a-3p targets MAD2L1 and regulates proliferation of gastric cancer cells[J]. Onco Targets Ther, 2019, 12: 11313-11324. doi: 10.2147/OTT.S222854.
[24] Ding X, Duan H, Luo H. Identification of core gene expression signature and key pathways in colorectal cancer[J]. Front Genet, 2020, 11: 45. doi: 10.3389/fgene.2020.00045.
[25] Niu Y, Wang Z, Huang H, et al. Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest[J]. Cancer Lett, 2014, 347(1): 88-97.
[26] Wang L, Wang J, Jin Y, et al. Downregulation of Mad2 and BubR1 increase the malignant potential and nocodazole resistance by compromising spindle assembly checkpoint signaling pathway in cervical carcinogenesis[J]. J Obstet Gynaecol Res, 2019, 45(12): 2407-2418.
[27] Dobles M, Liberal V, Scott ML, et al. Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2[J]. Cell, 2000, 101(6): 635-645.
[28] Jia D, Li S, Li D, et al. Mining TCGA database for genes of prognostic value in glioblastoma microenvironment[J]. Aging(Albany NY), 2018, 10(4): 592-605.
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