EB病毒感染对结直肠癌患者癌组织TLR4/MyD88信号通路影响

Effects of Epstein-Barr virus infection on TLR4/MyD88 signaling pathway in cancer tissues of patients with colorectal cancer

目的探讨EB病毒(EBV)感染对结直肠癌(CRC)患者癌组织Toll-样受体4/髓样分化蛋白抗原88(TLR4/MyD88)信号通路表达的影响。方法选择2017年6月-2020年8月在医院接受手术治疗的31例EBV阳性CRC患者为EBV阳性组,以同期收治的124例EBV阴性CRC患者为EBV阴性组。记录所有患者年龄、肿瘤直径、肿瘤分化程度、肿瘤浸润深度、TNM分期、淋巴结转移等临床特征。酶联免疫吸附试验检测血清白细胞介素-6(IL-6)、IL-8、IL-2和肿瘤坏死因子-α(TNF-α)水平,蛋白免疫印迹法检测癌组织和癌旁组织TLR4/MyD88信号通路表达。结果CRC患者癌组织中TLR4和MyD88蛋白表达高于癌旁组织(P<0.05);癌组织EBV阳性组CRC患者的肿瘤浸润深度侵入浆膜、TNM分期为Ⅲ期~Ⅳ期和合并淋巴结转移所占比例高于EBV阴性组(P<0.05),且EBV阳性组癌组织TLR4、MyD88、p-IκB和NF-κB p65蛋白表达水平高于EBV阴性组(P<0.05),血清IL-6、IL-8和TNF-α水平高于EBV阴性组(P<0.05),IL-2水平低于EBV阴性组(P<0.05)。结论EBV感染可以促进CRC患者癌组织TLR4/MyD88信号通路表达,促进CRC的恶性进展。

OBJECTIVE To explore the effects of Epstein-Barr virus(EBV)infection on the expression of Toll-like receptor 4/myeloid differentiation protein antigen 88(TLR4/MyD88)signaling pathway in cancer tissues of patients with colorectal cancer(CRC).METHODS The 31 EBV-positive CRC patients who underwent surgical treatment in the hospital from Jun 2017 to Aug 2020 were enrolled as the EBV-positive group,while another 124 EBV-negative CRC patients admitted during the same period were enrolled as the EBV-negative group.The clinical characteristics such as age,tumor diameter,tumor differentiation degree,tumor invasion depth,TNM staging and lymph node metastasis were recorded.The levels of serum interleukin 6(IL-6),IL-8,IL-2 and tumor necrosis factorα(TNF-α)were detected by enzyme-linked immunosorbent assay.The expression of TLR4/MyD88 signaling pathway in cancer tissues and para-carcinoma tissues was detected by Western Blot.RESULTS The expression of TLR4 and MyD88 in cancer tissues was significantly higher than that in para-carcinoma tissues(P<0.05).The proportion of tumor invasion depth into serosal membrane,TNM stageⅢ~Ⅳand lymph node metastasis in the EBV positive group CRC patients was significantly higher than that in the EBV negative group(P<0.05).The expression levels of TLR4,MyD88,p-IκB and NF-κB p65 proteins in the EBV-positive group were significantly higher than those in the EBV-negative group(P<0.05);levels of serum IL-6,IL-8 and TNF-αwere significantly higher than those in the EBV-negative group(P<0.05),while IL-2 level was significantly lower than that in the EBV-negative group(P<0.05).CONCLUSION EBV infection can promote the expression of TLR4/MyD88 signaling pathway in cancer tissues of CRC patients,and promote the malignant progression of CRC.