山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (10): 99-109.doi: 10.6040/j.issn.1671-7554.0.2022.0265
修德健1,2,高正文3,宋婷婷4,崔楠5,崔静6,孙健平6
XIU Dejian1,2, GAO Zhengwen3, SONG Tingting4, CUI Nan5, CUI Jing6, SUN Jianping6
摘要: 目的 通过TCGA和GEO数据库筛选与宫颈癌相关的关键基因,探讨其分子机制及临床意义。 方法 通过TCGA和GEO数据库获取宫颈癌的基因表达谱数据,采用加权基因共表达网络分析(WGCNA)获取宫颈癌与正常宫颈组织差异表达基因(DEGs),对DEGs进行富集分析、蛋白-蛋白互作网络(PPI)分析并识别关键基因,进一步对关键基因与预后及蛋白表达、以及与宫颈癌免疫浸润的关系进行分析。 结果 通过TCGA与GEO数据库中共得到88个宫颈癌DEGs,GO分析发现大部分基因与核染色体减速分裂、核染色体分裂、染色体集缩、核染色体等相关;KEGG信号通路分析发现宫颈癌DEGs参与了细胞周期、DNA复制、卵母细胞减数分裂、p53信号通路、同源重组等信号通路。鉴定出20个宫颈癌关键基因,仅有丝分裂阻滞缺陷2样蛋白1(MAD2L1)低表达患者的总生存期(OS)长于MAD2L1高表达患者(P=0.013),但MAD2L1高表达患者的无病生存期(DFS)与低表达患者差异无统计学意义(P>0.05),宫颈癌组织中MAD2L1蛋白高于正常组织。TIMER在线软件分析显示,MAD2L1与肿瘤的免疫浸润水平均相关(P<0.05)。 结论 发现了与宫颈癌相关的候选基因MAD2L1,其与宫颈癌患者的预后及免疫浸润均有关,可能成为宫颈癌预后预测及治疗的新靶点。
中图分类号:
[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. |
[1] | 李琳琳,王凯. 基于生物信息学预测肝细胞癌预后基因[J]. 山东大学学报 (医学版), 2022, 60(5): 50-58. |
[2] | 陈泉材,韩赛,刘露,孙雨,尤学武,张俊华,张友忠. CDC7、MCM4在105例宫颈病变组织中的表达及意义[J]. 山东大学学报 (医学版), 2022, 60(1): 34-39. |
[3] | 王璐,赵新蕊,朱琳. 25例早期宫颈癌无瘤化免举宫腹腔镜子宫切除术临床效果[J]. 山东大学学报 (医学版), 2021, 59(6): 76-80. |
[4] | 耿晨,杨阳,赵月,刘浩冉,晁岚. 子宫腺肌病中差异基因筛选及Wilms tumor-1的表达[J]. 山东大学学报 (医学版), 2021, 59(4): 79-86. |
[5] | 孔雪,李娟,段伟丽,史爽,李培龙,杜鲁涛,毛海婷,王传新. 长链非编码RNA AC012073.1对乳腺癌细胞迁移侵袭的影响及临床价值[J]. 山东大学学报 (医学版), 2021, 59(4): 70-78. |
[6] | 华芳,张薇薇,吕波,辛玮. 生物信息学分析骨关节炎滑膜炎症相关基因和分子途径[J]. 山东大学学报 (医学版), 2021, 59(3): 10-17. |
[7] | 梁婷婷,杨勇霞,侯丛哲,黄太胜,王华丽,朱琳. PAX1基因甲基化与宫颈高级别上皮内病变及高危型HPV分型的关联性[J]. 山东大学学报 (医学版), 2021, 59(11): 48-52. |
[8] | 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. |
[9] | 陈颖,周小青,齐眉,张魏芳,刘娟,赵蔚明. 干扰PRPS2基因表达对宫颈癌细胞生物学特性的影响[J]. 山东大学学报 (医学版), 2018, 56(2): 9-13. |
[10] | 王传新. 外泌体生物标志物与肿瘤发生发展的研究进展[J]. 山东大学学报 (医学版), 2018, 56(10): 18-23. |
[11] | 王红阳. 精准医疗时代的肿瘤生物标志物发展[J]. 山东大学学报 (医学版), 2018, 56(10): 1-2. |
[12] | 王永,姜晨,周士英,杨晓玫. IQ结构域GTP酶激活蛋白3表达对宫颈癌细胞增殖和转移的影响[J]. 山东大学学报 (医学版), 2018, 56(10): 103-109. |
[13] | 丁长宽,陈健行. 蛋白酶体抑制剂硼替佐米联合顺铂对宫颈癌细胞增殖的影响[J]. 山东大学学报 (医学版), 2018, 56(1): 70-75. |
[14] | 刘京康,杨建勇,孟丽华,姜洁. 血清miR-17-92簇在HPV阳性宫颈癌中的早期诊断价值[J]. 山东大学学报(医学版), 2017, 55(5): 86-90. |
[15] | 孙泽雨,陈颖,林家香,刘娟,赵蔚明. 磷脂酰肌醇-4-磷酸酶II型对宫颈癌细胞增殖及凋亡的影响[J]. 山东大学学报(医学版), 2017, 55(11): 1-6. |
|