TLR4、MyD88和ERK1/2表达与EB病毒感染结肠癌的相关性

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。

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

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.