您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (7): 75-79.doi: 10.6040/j.issn.1671-7554.0.2015.1131

• • 上一篇    下一篇

TLR4、MyD88和ERK1/2表达与EB病毒感染结肠癌的相关性

曹楷,王超群,郑茂金,吴永平   

  1. 徐州医学院临床与实验病理教研室, 江苏 徐州 221004
  • 收稿日期:2015-11-19 出版日期:2016-07-10 发布日期:2016-07-10
  • 通讯作者: 吴永平. E-mail:wyp@xzmc.edu.cn E-mail:wyp@xzmc.edu.cn

Correlation between TLR4, MyD88 and ERK1/2 expressions and EBV infected colorectal cancer

CAO Kai, WANG Chaoqun, ZHENG Maojin, WU Yongping   

  1. Department of Pathology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China
  • Received:2015-11-19 Online:2016-07-10 Published:2016-07-10

摘要: 目的 探讨TLR4、MyD88和ERK1/2的表达与EB病毒感染结直肠癌的相关性。 方法 通过336例结直肠癌和103例正常肠黏膜组织制备组织芯片,运用原位分子杂交检测EBER表达,分析EBER表达与结肠癌患者临床病理参数及预后的相关性,并用免疫组化SP法检测TLR4、MyD88和ERK1/2表达,分析三因子与EB病毒感染结直肠癌的相关性。 结果 在336例结直肠癌患者中,TLR4、 MyD88、ERK1/2、EBER阳性均较正常黏膜组(对照组)升高(P<0.05)。EBER阳性与女性、浸润浆膜、有淋巴结转移和临床TNM Ⅲ、Ⅳ 分期呈正相关(P<0.05)。对336例结直肠癌患者预后分析发现EBER阳性与患者无病生存率和总生存率低水平密切相关(P<0.05)。同时,在25例EBER阳性结直肠癌组织中,TLR4、MyD88、ERK1/2分别在22例(P=0.025)、25例(P=0.028)、19例(P=0.092)中阳性表达。 结论 EB病毒感染阳性与结直肠癌进展密切相关,特别是女性患者是影响患者预后的独立危险因素。TLR4、MyD88表达上调可能在EB病毒感染结直肠癌中发挥重要作用。

关键词: 爱泼斯坦-巴尔病毒, Toll样受体4, 结肠直肠肿瘤, 细胞外信号调节激酶, 髓样分化因子88

Abstract: Objective To explore the correlation between toll-like receptor 4(TLR4), myeloid differentiation primary response gene 88(MyD88)and extracellular signal-regulated protein kinases 1 and 2(ERK1/2)expressions and Epstein-Barr virus(EBV)infection in colorectal cancer. Methods Epstein-Barr virus-encoded small RNA(EBER)expression was detected by in situ hybridization using microarray chips containing tissues from 336 cases of colorectal cancer and 103 cases of normal mucosa. The correlation between EBER expression and clinicopathological parameters and prognosis of colorectal cancer was analyzed. Additionally, TLR4, MyD88 and ERK1/2 expressions were detected using SP immunohistochemistry. The correlation between these three factors and EBV infection in colorectal cancer was analyzed. Results TLR4, MyD88, ERK1/2 and EBER expressions were increased in the 336 cases of colorectal cancer compared to the controls(P<0.05). EBER expression was positively correlated with the female gender, serosal infiltration, lymph node metastasis and clinical TNM stages Ⅲ and Ⅳ(P<0.05). Prognostic analysis of the 336 cases of colorectal cancer demonstrated that EBER expression was closely associated with low disease-free survival and overall survival rates(P<0.05). In addition, TLR4, MyD88 and ERK1/2 were expressed in 22(P=0.025), 25(P=0.028)and 19(P=0.092)of the 25 EBER-positive colorectal cancer tissues, respectively. Conclusion EBV infection is closely associated with the progress of colorectal cancer, particularly in female patients, and represents an independent risk factor for the prognosis. Upregulation of TLR4 and MyD88 expressions may play an important role in EBV infected colorectal cancer.

Key words: Colorectal neoplasm, Epstein-barr virus, Myeloid differentiation factor 88, Toll-like receptor 4, Extracellular regulated kinase

中图分类号: 

  • R735.3
[1] 李增山, 李青. 2010年版消化系统肿瘤WHO分类解读[J]. 中华病理学杂志, 2011, 40(5): 351-354. LI Zengshan, LI Qing. The latest 2010 WHO classification of tumors of digestive system[J]. Zhonghua Bing Li Xue Za Zhi, 2011, 40(5): 351-354.
[2] 陈万青, 郑荣寿, 曾红梅, 等. 2011年中国恶性肿瘤发病和死亡分析[J].中国肿瘤, 2015, 24(1): 1-10. CHEN Wanqing, ZHENG Rongshou, ZENG Hongmei, et al. Report of cancer incidence and mortality in China, 2011[J]. China Cancer, 2015, 24(1): 1-10.
[3] Andersson-Anvret M, Forsby N, Klein G, et al. Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination[J]. Int J Cancer, 1977, 20(4): 486-494.
[4] Gandhi MK, Tellam JT, Khanna R. Epstein-Barr virus-associated Hodgkins lymphoma[J]. Br J Haematol, 2004, 125(3): 267-281.
[5] Iizasa H, Nanbo A, Nishikawa J, et al. Epstein-Barr virus(EBV)-associated gastric carcinoma[J]. Viruses, 2012, 4(12): 3420-3439.
[6] Liu HX, Ding YQ, Li X, et al. Investigation of Epstein-Barr virus in Chinese colorectal tumors[J]. World J Gastroenterol, 2003, 9(11): 2464-2468.
[7] Thorley-Lawson DA. EBV the prototypical human tumor virus-just how bad is it?[J]. J Allergy Clin Immunol, 2005, 116(2): 251-261.
[8] Coleman CB, Wohlford EM, Smith NA, et al. Epstein-Barr virus type 2 latently infects T cells, inducing an atypical activation characterized by expression of lymphotactic cytokines[J]. J Virol, 2015, 89(4): 2301-2312.
[9] Wu HC, Lin YJ, Lee JJ, et al. Functional analysis of EBV in nasopharyngeal carcinoma cells[J]. Lab Invest, 2003, 83(6): 797-812.
[10] Wang M, Yang W, Li M, et al. Low expression of miR-150 in pediatric intestinal Burkitt lymphoma[J]. Exp Mol Pathol, 2014, 96(2): 261-266.
[11] Tafvizi F, Fard ZT, Assareh R. Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients[J]. Pol J Pathol, 2015, 66(2): 154-160.
[12] Lim H, Park YS, Lee JH, et al. Features of gastric carcinoma with lymphoid stroma associate with Epstein-Barr virus[J]. Clin Gastroenterol Hepatol, 2015, 13(10): 1738-1744.
[13] Zheng X, Xie J, Zhou X. Epstein-Barr virus associated T-cell lymphoproliferative disease misdiagnosed as ulcerative colitis: a case report[J]. Int J Clin Exp Pathol, 2015, 8(7): 8598-8602.
[14] Wang LT, Lin CS, Chai CY, et al. Functional interaction of Ugene and EBV infection mediates tumorigenic effects[J]. Oncogene, 2011, 30(26): 2921-2932.
[15] Lai KY, Chou YC, Lin JH, et al. Maintenance of Epstein-Barr virus latent status by a novel mechanism, latent membrane protein 1-induced interleukin-32, via the protein kinase CδPathway[J]. J Virol, 2015, 89(11): 5968-5980.
[16] Harsini S, Beigy M, Akhavan-Sabbagh M, et al. Toll-like receptors in lymphoid malignancies: double-edged sword[J]. Crit Rev Oncol Hematol, 2014, 89(2): 262-283.
[17] Wang EL, Qian ZR, Nakasono M, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer[J]. Br J Cancer, 2010, 102(5): 908-915.
[18] Zhang L, Ji Q, Liu X, et al. Norcantharidin inhibits tumor angiogenesis via blocking VEGFR2/MEK/ERK1/2 signaling pathways[J]. Cancer Sci, 2013, 104(5): 604-610.
[19] Huang B, Zhao J, Li H, et al. Toll-like receptors on tumor cells facilitate evasion of immune surveillance[J]. Cancer Res, 2005, 65(12): 5009-5014.
[20] Rakoff-Nahoum S, Medzhitov R. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88[J]. Science, 2007, 317(5834):124-127.
[1] 付洁琦,张曼,张晓璐,李卉,陈红. Toll样受体4抑制过氧化物酶体增殖物激活受体γ加重血脂蓄积的分子机制[J]. 山东大学学报 (医学版), 2020, 1(7): 24-31.
[2] 巨媛媛,任满意,李睿,赵萌萌,隋树建. TWEAK通过ERK1/2通路促进大鼠心肌成纤维细胞MMP2与Ⅰ型胶原表达[J]. 山东大学学报(医学版), 2016, 54(5): 23-28.
[3] 李涛, 吴洪喜, 张永超, 郑志明, 张振, 滕良珠. 氯化两面针碱对垂体腺瘤GH3细胞的抑制作用[J]. 山东大学学报(医学版), 2015, 53(10): 6-10.
[4] 李悦妍1,关玉庆2,苗伟2,户克庆2,胡鸿雁3,李莹2,王晓琦2,苏国海2. 阿托伐他汀对动脉粥样硬化模型兔toll样受体4及其下游信号表达的影响[J]. 山东大学学报(医学版), 2014, 52(6): 1-6.
[5] 丁超, 胡启雅, 黄海真, 郭亚秋, 裴淼, 朱庆增, 齐峰. 倍他米松二丙酸酯缓释微球对大鼠神经病理性疼痛的镇痛作用及对脊髓细胞外信号调节激酶的影响[J]. 山东大学学报(医学版), 2014, 52(10): 35-39,44.
[6] 牟乐明1,孙占胜1,王伯珉1,高平2,初向全3. 骨髓间充质干细胞移植对脊髓损伤大鼠Toll样受体4表达的影响[J]. 山东大学学报(医学版), 2014, 52(1): 37-41.
[7] 彭笑怒1,2,李文军2,田辉1. 抑制聚二磷酸腺苷核糖聚合酶1减轻尼古丁诱导的支气管上皮细胞炎症反应[J]. 山东大学学报(医学版), 2013, 51(2): 37-43.
[8] 王雪芹1,岳忠勇2,李克忠1,马金凤1. 周期性机械牵张对大鼠肺泡巨噬细胞TLR4表达的影响[J]. 山东大学学报(医学版), 2013, 51(06): 40-43.
[9] 程兆令,李雪梅,杨廷廷,朱强. 结直肠癌中TLR4的表达及其与FasL、EGFR的关系[J]. 山东大学学报(医学版), 2012, 50(5): 92-.
[10] 刘胜楠,卢雪峰,孙娜,郑雪婷,李倩倩. Toll样受体2、4及核因子-κB在溃疡性结肠炎黏膜组织中的表达及临床意义[J]. 山东大学学报(医学版), 2012, 50(2): 60-.
[11] 王志强1,2,于振海2,袁方曙1. 双歧杆菌对溃疡性结肠炎大鼠肠黏膜上皮细胞Toll样受体2、4及NF-κB基因表达的影响[J]. 山东大学学报(医学版), 2011, 49(5): 10-14.
[12] 张学平,王莉,龙飞,李怀臣. 黄芪多糖抑制气道平滑肌细胞α-SMA的表达[J]. 山东大学学报(医学版), 2011, 49(2): 79-.
[13] 邢姗姗1,张伟2,宫玉玲3,王东4,李国华3,邢启崇3. Toll样受体4与冠状动脉病变的关系[J]. 山东大学学报(医学版), 2011, 49(11): 69-.
[14] 韩业明,姜士芹,张超. ISO-1对人脐静脉内皮细胞Toll样受体4活性的调节及意义[J]. 山东大学学报(医学版), 2010, 48(8): 65-69.
[15] 宫玉玲1,2,邢姗姗3,张伟4,邢启崇1,2. Toll样受体4与动脉粥样硬化的关系[J]. 山东大学学报(医学版), 2010, 48(3): 127-130.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!