山东大学耳鼻喉眼学报 ›› 2021, Vol. 35 ›› Issue (5): 75-84.doi: 10.6040/j.issn.1673-3770.0.2021.068

• • 上一篇    下一篇

复发性喉乳头状瘤中潜在生物学标志物的筛选及生物信息学分析

齐雯雯1,陈鲁秋2,贾涛1,陈雪梅1,张杰1,张皓1,金鹏1,张虎3   

  1. 1. 山东大学第二医院 耳鼻咽喉头颈外科, 山东 济南 250033;
    2. 山东大学齐鲁医院 小儿外科, 山东 济南 250012;
    3. 济南市章丘区人民医院 耳鼻喉科, 山东 济南 250200
  • 发布日期:2021-09-29
  • 通讯作者: 张虎. E-mail:Zq3250942@sina.com
  • 基金资助:
    山东省重点研发计划(2018GSF118091)

Potential biomarkers and bioinformatics analysis of differentially expressed genes in recurrent laryngeal papilloma

QI Wenwen1, CHEN Luqiu2, JIA Tao1, CHEN Xuemei1, ZHANG Jie1, ZHANG Hao1, JIN Peng1, ZHANG Hu3   

  1. 1. Department of Otorhinolaryngology & Head and Neck Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong, China;
    2. Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    3. Department of Otolaryngology, Jinan Zhangqiu District People's Hospital, Jinan 250200, Shandong, China
  • Published:2021-09-29

PDF (PC)

153

摘要： 目的 通过生物信息学技术筛选复发性喉乳头状瘤中表达的差异基因,为复发性喉乳头状瘤的治疗提供新的思路和靶点。 方法 从GEO数据库下载复发性喉乳头状瘤的芯片数据集GSE10935,使用在线分析工具GEO2R筛选复发性喉乳头状瘤及其相邻正常喉黏膜组织间的差异表达基因,使用网络分析工具Metascape进行差异基因的GO分析及KEGG通路富集,通过STRING在线软件进行差异表达基因的蛋白-蛋白相互作用分析,并应用Cytoscape对蛋白-蛋白相互作用网络进行模块分析。最后,使用转录因子富集分析数据库ChEA3预测复发性喉乳头状瘤组织中差异表达基因的关键转录因子。 结果 在10对复发性喉乳头状瘤组织及其相邻的正常喉黏膜组织间共筛选出53个差异表达基因(DEGs)(|logFC|>1,adj P<0.05),其中上调的DEGs共30个,下调的DEGs共23个。GO分析和KEGG通路富集显示,这些差异表达的基因主要富集在多个代谢、免疫调节及PPAR信号通路等。通过蛋白-蛋白相互作用网络的构建及模块分析,筛选出SLC27A2、SCD、ECI2及FADS2四个枢纽差异表达基因。进一步的分析发现,TP63为复发性喉乳头状瘤中最为重要的转录因子。 结论 为进一步深入理解复发性喉乳头状瘤的生物学机制、探索其治疗的有效方案提供了新思路。

关键词: 喉乳头状瘤, 复发, 差异表达基因, 生物信息学分析

Abstract: Objective This study aimed to provide new ideas or targets for recurrent laryngeal papilloma using bioinformatics. Methods The chip dataset GSE10935 was downloaded from the Gene Expression Omnibus(GEO)database, and the online analysis tool GEO2R was used to screen differentially expressed genes(DEGs)between recurrent laryngeal papilloma tissues and their adjacent normal laryngeal mucosal tissues. Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of the DEGs were performed using the online software Metascape. The STRING online software was used to analyze the protein interactions of the DEGs. Module analysis of the hub genes was performed using the Cytoscape software. Finally, the online transcription factor enrichment analysis database CHEA3 was used to predict the key transcription factors in recurrent laryngeal papilloma tissues. Results A total of 53 DEGs(|logFC|>1, adj P<0.05)including 30 upregulated and 23 down-regulated genes were screened from 10 pairs of recurrent laryngeal papilloma tissues and their adjacent normal laryngeal mucosal tissues. GO and KEGG pathway enrichment analyses suggested that these DEGs were mainly enriched in multiple metabolic processes, including immunomodulation and PPAR signaling pathways. SLC27A2, SCD, ECI2 and FADS2 were screened as the hub genes through protein-protein interaction network construction and module analysis. Further analysis revealed that TP63 was the most important transcription factor in recurrent laryngeal papilloma. Conclusion This study provides new ideas for in-depth understanding of the biological mechanism of recurrent laryngeal papilloma and exploring effective treatment for recurrent laryngeal papilloma.

Key words: Laryngeal papilloma, Recurrent, Differentially expressed genes, Bioinformatics analysis

中图分类号: 

  • R767.1
[1] Makiyama K, Hirai R, Matsuzaki H, et al. Assessment of human Papilloma virus infection in adult laryngeal Papilloma using a screening test[J]. J Voice, 2013, 27(2):230-235. doi:10.1016/j.jvoice.2012.10.014.
[2] 孙睿杰,许风雷,刘大昱,等.显微支撑喉镜下CO2激光手术或联合干扰素治疗复发性小儿喉乳头状瘤疗效对比[J].山东大学耳鼻喉眼学报, 2012, 26(6):23-25. doi:10.6040/j.issn.1673-3770.2012.06.008. SUN Ruijie, XU Fenglei, LIU Dayu, et al. Efficacy of CO2 laser surgery under microsupport laryngoscope or combined with interferon in the treatment of recurrent laryngeal papilloma in children[J]. J Otolaryngol Ophthalmol Shandong Univ, 2012, 26(6):23-25. doi:10.6040/j.Issn.1673-3770.2012.06.008.
[3] Fortes HR, von Ranke FM, Escuissato DL, et al. Recurrent respiratory papillomatosis:a state-of-the-art review[J]. Respir Med, 2017,126:116-121. doi:10.1016/j.rmed.2017.03.030.
[4] Langer C,Wittekindt C, Wolf G. Rezidivierende respiratorische Papillomatose: Aktuelles zu Diagnose und Therapie[J]. Onkologie Up2date, 2020, 2(2):107-118. doi:10.1055/a-1132-0051.
[5] 申宇鹏,宋琦,李晓明.喉癌前病变的病因、分子机制和处理策略[J].山东大学耳鼻喉眼学报, 2019, 33(4):25-30. doi: 10.6040 /j.Issn.1673-3770.1.2019.029. SHEN Yupeng, SONG Qi, LI Xiaoming. Etiology, molecular mechanisms, and treatment strategies of precancerous laryngeal lesions[J]. J Otolaryngol Ophthalmol Shandong Univ, 2019, 33(4): 25-30. doi: 10.6040 /j.Issn.1673-3770.1.2019.029.
[6] 张群慧,龚辉成,林颖,等.喉癌高危型人乳头状瘤病毒检测及表皮生长因子受体表达的研究[J].中国耳鼻咽喉头颈外科,2019,26(8):429-431. doi:10.16066/j.1672-7002.2019.08.007. ZHANG Qunhui, GONG Huicheng, LIN Ying, et al. Study of the detection of high risk HPV and EGFR expression in laryngeal cancer[J]. ChinArch Otolaryngol-Head Neck Surg, 2019, 26(8): 429-431. doi:10.16066/j.1672-7002.2019.08.007.
[7] 雷文斌,刘其洪. CO2激光手术治疗复发性呼吸道乳头状瘤[J].山东大学耳鼻喉眼学报, 2018, 32(6):8-12. doi: 10.6040 /j.Issn.1673-3770.1.2018.014. LEI Wenbin, LIU Qihong. Progress in the treatment of recurrent respiratory papillomatosis using a CO2 laser[J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(6),32:8-12. doi: 10.6040 /j.Issn.1673-3770.1.2018.014.
[8] 潘晓菲,王军,肖洋,等.LncRNA CTB-147C22.8 对复发性呼吸道乳头状瘤细胞侵袭的影响[J].山东大学耳鼻喉眼学报,2019,33(4):66-70. doi: 10.6040 /j.Issn.1673-3770.0.2018.409. PAN Xiaofei, WANG Jun, XIAO Yang, et al. Effect of lncRNA cTB-147C28.8 on the invasion of recurrent respiratory papilloma cells[J]. J Otolaryngol Ophthalmol Shandong Univ, 2019, 33(4):66-70. doi: 10.6040 /j.Issn.1673-3770.0.2018.409.
[9] Reeves WC, Ruparelia SS, Swanson KI, et al. National registry for juvenile-onset recurrent respiratory papillomatosis[J]. Arch Otolaryngol-Head Neck Surg, 2003,129(9): 976-982. doi:10.1001/archotol.129.9.976.
[10] Murali S, Saravanam PK, Dinakaran N. Role of Thuja in the management of laryngeal Papilloma[J]. BMJ Case Rep, 2020,13(12):e238846. doi:10.6040/j.Issn.1673-3770.0.2015.007.
[11] 严羽,朱江.早期喉癌及喉癌前病变诊断的研究进展[J].山东大学耳鼻喉眼学报,2015,29(4):80-85. doi:10.6040 /j.issn.1673-3770.0.2015.007. SHEN Yupeng, SONG Qi, LI Xiaoming. Etiology, molecular mechanisms, and treatment strategies of precancerous laryngeal lesions[J]. J Otolaryngol Ophthalmol Shandong Univ, 2019, 33(4):25-30. doi:10.6040 /j.Issn.1673-3770.0.2015.007.
[12] 张再兴,薛丽华.喉乳头状瘤的病因学机制及防治[J].山东大学耳鼻喉眼学报, 2005, 19(6): 409-411. doi:10.3969/j.issn.1673-3770.2005.06.024. ZHANG Zaixing, XUE Lihua[J]. J Otolaryngol Ophthalmol Shandong Univ,2005,19(6): 409-411. doi:10.3969/j.issn.1673-3770.2005.06.024.
[13] Liu J, Yang T, Zhang Y, et al. Promotion of BZW2 by LINC00174 through miR-4500 inhibition enhances proliferation and apoptosis evasion in laryngealPapilloma[J]. Cancer Cell Int, 2020, 20:471. doi:10.1186/s12935-020-01559-3.
[14] Lai EC. Two decades of miRNA biology: lessons and challenges[J]. RNA, 2015, 21(4):675-677. doi:10.1261/rna.051193.115.
[15] Guo H, Qi RQ, Sheng J, et al. MiR-155, a potential serum marker of extramammary Paget's disease[J]. BMC Cancer, 2018, 18(1):1078. doi:10.1186/s12885-018-4994-1.
[16] 徐颖誉.FADS2 rs3834458基因多态性与中国汉族人群非酒精性脂肪性肝病合并冠心病易感性研究[D].青岛:青岛大学,2019. doi:10.27262/d.cnki.gqdau.2019.001527. XU Yingyu. FADS2 rs3834458 gene polymorphism and susceptibility to non-alcoholic fatty liver disease complicated with coronary heart disease in Chinese Han population[D]. Qingdao: Qingdao University, 2019. doi:10.27262/d.cnki.gqdau.2019.001527.
[17] Matsumoto A, Kawabata T, Kagawa Y, et al. Associations of umbilical cord fatty acid profiles and desaturase enzyme indices with birth weight for gestational age in Japanese infants[J]. Prostaglandins Leukot Essent Fatty Acids, 2021,165:102233. doi:10.1016/j.plefa.2020.102233.
[18] 林智海,王正东,吴梓嘉,等.冠心病心绞痛患者倍他乐克联合阿司匹林治疗的有效性及对患者血清hs-CRP、sCD40L、IL-6水平的影响[J].临床和实验医学杂志, 2021, 20(3):259-262. doi:10.3969/j.Issn.1671-4695.2021.03.010. LIN Zhihai, WANG Zhengdong, WU Zijia, et al. Efficacy of betaloc combined with aspirin in patients with coronary heart disease and angina pectoris and its effect on serum hs-CRP, sCD40L and IL-6 levels[J]. Journal of Clinical and Experimental Medicine, 2021,20(3):259-262. doi:10.3969/j.Issn.1671-4695.2021.03.010.
[19] 曹白鸽,刘冲霄,陈源文,等.IL-6上调SCD1表达对HepG2细胞脂质合成功能的影响[J]. 实用肝脏病杂志, 2019, 22(2):172-175. doi:10.3969/j.issn.1672-5069.2019.02.005. CAO Baige, LIU Chongxiao, CHEN Yuanwen, et al. Upregulation of SCD1 gene-related lipid synthesis by IL-6 stimulus in HepG2 cells in vitro[J]. J Pract Hepatol, 2019, 22(2):172-175. doi:10.3969/j.issn.1672-5069.2019.02.005.
[20] Chen FD, Chen HH, Ke SC, et al. SLC27A2 regulates miR-411 to affect chemo-resistance in ovarian cancer[J]. Neoplasma, 2018,65(6): 915-924. doi:10.4149/neo_2018_180122n48.
[21] Feng Y, Li S, Zhang R, et al. FOXM1 as a prognostic biomarker promotes endometrial cancer progression via transactivation of SLC27A2 expression[J]. Int J Clin Exp Pathol, 2018,11(8):3846-3857. doi:1936-2625/IJCEP0081131.
[22] Dan C, Zhang HY, Zeng WJ, et al. HNF1B expression regulates ECI2 gene expression, potentially serving a role in prostate cancer progression[J]. Oncol Lett, 2019, 17(1):1094-1100. doi:10.3892/ol.2018.9677.
[23] DeVoti JA, Rosenthal DW, Wu R, et al. Immune dysregulation and tumor-associated gene changes in recurrent respiratory papillomatosis: a paired microarray analysis[J]. Mol Med, 2008,14(9/10): 608-617. doi:10.2119/2008-00060.devoti.
[24] 郭正平,张红.小儿喉乳头状瘤HPV感染与免疫功能变化的关系研究[J]. 华南国防医学杂志, 2020, 34(1):37-40. doi:10.13730/j.issn.1009-2595.2020.01.009. GUO Zhengping, ZHANG Hong. Correlation between HPV infection and immune function changes in children with laryngeal Papilloma[J]. Mil Med J South China, 2020, 34(1):37-40. doi:10.13730/j.issn.1009-2595.2020.01.009.
[25] Sasaki E, Masago K, Fujita S, et al. Frequent KRAS and HRAS mutations in squamous cell papillomas of the head and neck[J]. J Pathol Clin Res, 2020, 6(2):154-159. doi:10.1002/cjp2.157.
[26] Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020[J]. Rhinology, 2020, 20(58):1-464. doi:10.4193/Rhin20.600.
[27] Han L, Shen WJ, Bittner S, et al. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α[J]. Future Cardiol. 2017,13(3):279-296. doi:10.2217/fca-2016-0059.
[28] Caillaud M, Patel NH, Toma W, et al. A fenofibrate diet prevents paclitaxel-induced peripheral neuropathy in mice[J]. Cancers, 2020, 13(1): 69. doi:10.3390/cancers13010069.
[29] Liu X, Qian D, Liu H, et al. Genetic variants of the peroxisome proliferator-activated receptor(PPAR)signaling pathway genes and risk of pancreatic cancer[J]. Mol Carcinog, 2020,59(8):930-939. doi:10.1002/mc.23208.
[30] Brunetti L, Loiodice F, Piemontese L, et al. New approaches to cancer therapy: combining fatty acid amide hydrolase(FAAH)inhibition with peroxisomeproliferator-activated receptors(PPARs)activation[J]. J Med Chem, 2019, 62(24): 10995-11003. doi:10.1021/acs.jmedchem.9b00885.
[31] Halstead AM, Kapadia CD, Bolzenius J, et al. Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation[J]. Elife, 2017,6: e30862. doi:10.7554/eLife.30862.
[32] Yi M, Tan Y, Wang L, et al. TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development[J]. Cell Mol Life Sci, 2020,77(21):4325-4346. doi:10.1007/s00018-020-03539-2.
[33] 郑雪. TP63基因启动子DNA甲基化与宫颈癌的相关性研究[D]. 唐山: 华北理工大学, 2020.
[34] 魏涛,朱精强. p53 基因家族与甲状腺癌的相关研究进展[J]. 中国普外基础与临床杂志,2019, 26(11):1372-1377. doi:10.7507/1007-9424.201906054. WEI Tao, ZHU Jingqiang. Advances of relationship between p53 gene family and thyroid cancer. Chinese Journal of Bases and Clinics in General Surgery, 2019, 26(11):1372-1377. doi:10.7507/1007-9424.201906054.
[35] 冯志寅, 王维娜, 董娟娟, 等. P53、P63、Ki67分子标记物与食管癌淋巴结转移相关性Logistic回归分析[J]. 新疆医科大学学报, 2015,38(9): 1091-1094,1098. doi:10.3969/j.issn.1009-5551.2015.09.007. FENG Zhiyin, WANG Weina, DONG Juanjuan, et al. Logistic regression analysis on relationship between P53 P63 Ki67 expression and lymph node metastasis in esophageal carcinoma[J]. J Xinjiang Med Univ, 2015,38(9): 1091-1094,1098.doi:10.3969/j.issn.1009-5551.2015.09.007.
[36] 于克娜, 孙凯月, 张杰, 等. 西妥昔单抗治疗头颈部鳞状细胞癌差异表达基因的生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2020,34(4): 117-124. doi: 10.6040 /j.Issn.1673-3770.0.2020.189. YU Kena, SUN Kaiyue, ZHANG Jie, et al. Analysis of differentially expressed genes during cetuximab treatment of head and neck squamous cell carcinoma using bioinformatics[J]. J Otolaryngol Ophthalmol Shandong Univ, 2020,34(4): 117-124. doi: 10.6040 /j.Issn.1673-3770.0.2020.189.
[1] 牛子捷,肖洋王军,马丽晶. 喉乳头状瘤手术治疗的研究进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 96-100.
[2] 范黎,黎越,徐细明. 鼻咽癌同步放化疗前后炎性指标变化及预测价值[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 36-41.
[3] 陈建勇, 孙夏雨, 沈佳丽, 汪玮, 王璐, 贺宽, 张勤, 马孝宝, 沈敏, 陈向平, 杨军. 原发性良性阵发性位置性眩晕患者VEMP异常率的临床观察[J]. 山东大学耳鼻喉眼学报, 2020, 34(5): 51-55.
[4] 于克娜,孙凯月,张杰,金鹏. 西妥昔单抗治疗头颈部鳞状细胞癌差异表达基因的生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(4): 117-124.
[5] 吕静荣,陈淳,马衍,谢晋. 儿童分化型甲状腺癌的临床特征及危险因素分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(3): 88-94.
[6] 谢书华, 杨竹梅, 刘慧茹, 董晶. NLR、LMR、PLR预测慢性鼻窦炎鼻内镜术后复发价值[J]. 山东大学耳鼻喉眼学报, 2020, 34(1): 54-57.
[7] 潘晓菲,王军,肖洋,马丽晶. LncRNA CTB-147C22.8对复发性呼吸道乳头状瘤细胞侵袭的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 66-70.
[8] 陈慧君,宋圣花,周涵,董伟达,乔明哲,陈曦,徐进,林子萍,邢光前. 血小板与淋巴细胞比值对喉癌复发的预测价值[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 106-110.
[9] 姜彦. 鼻咽癌复发及鼻内镜外科手术的应用[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 1-11.
[10] 陈冬平,杨致欢,张炎,方楠,齐斌. 复发鼻咽癌手术治疗地位的思考[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 12-16.
[11] 徐文瑞,姜彦. 复发鼻咽癌挽救性手术方法研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 35-38.
[12] 刘冬梅,李洋,宋继科,郭大东,马先祯,毕宏生. 玻璃体切割联合硅油填充术后晶状体基因表达谱的变化及验证[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 95-98.
[13] 雷文斌,刘其洪. CO2激光手术治疗复发性呼吸道乳头状瘤[J]. 山东大学耳鼻喉眼学报, 2018, 32(6): 8-12.
[14] 伦杰,张亚楠. 慢性鼻-鼻窦炎伴鼻息肉复发的相关影响因素分析[J]. 山东大学耳鼻喉眼学报, 2017, 31(3): 80-83.
[15] 包伟晶,宁佳羽,朱忠寿,魏日富,林昶. CO2激光切除累及前联合的早期声门癌26例[J]. 山东大学耳鼻喉眼学报, 2016, 30(5): 101-105.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 张晗,黄一飞 . 抗角膜移植排斥的研究进展[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 84 -87 .
[2] 牛善利,柴茂文,李振秀 . 鼻内镜下鼻甲成形术治疗慢性肥厚性鼻炎60例[J]. 山东大学耳鼻喉眼学报, 2006, 20(1): 16 -18 .
[3] 孟庆国,卢永田,范献良 . 杀伤细胞免疫球蛋白样受体基因多态性与鼻咽癌的关联性[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 196 -199 .
[4] 马玉起,孔祥春 . 先天性双侧下唇窦道1例[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 199 -199 .
[5] 万俐佳,鲁海涛,姜义道,刘 辉,李 琴,佘腊枝 . 改良腭咽成形术治疗阻塞性睡眠呼吸暂停综合征41例[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 204 -205 .
[6] 于青青 ,王跃建 . 硬质耳内镜的临床应用进展[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 222 -224 .
[7] 吉晓滨,邓家德,臧林泉,王 磊,谢 军 . 豚鼠变应性鼻炎模型血清组胺的测定[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 228 -230 .
[8] 向登,卢永田,孙焕吉 . 鼻内镜下修补脑脊液鼻漏19例并文献复习[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 234 -236 .
[9] 邱恩惠,李志春,方文旭 . 嗅觉障碍的中西医治疗[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 253 -257 .
[10] 殷国华,钟 笑 . 激光减容术治疗舌扁桃体肥大的远期疗效[J]. 山东大学耳鼻喉眼学报, 2008, 22(3): 280 -282 .
网站版权所有 © 2018 《山东大学耳鼻喉眼学报》编辑部　
地址：山东省济南市山大南路27号（250100）电话：+86-0531-88366912 E-mail: ebhxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发