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目的研究有丝分裂原活化蛋白激酶激酶激酶(MEKK3)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)在宫颈病变组织中的表达及其相关性,分析其表达与宫颈癌临床病理特征及预后的关系。方法利用组织芯片技术构建宫颈病变芯片,应用免疫组化En Vision法检测107例宫颈癌、86例宫颈上皮内瘤变(CIN)及35例慢性宫颈炎组织中MEKK3和TRAIL表达水平,同时随访3年以上宫颈癌患者44例,进行生存分析。结果 MEKK3在慢性宫颈炎、宫颈CIN和宫颈癌组织中阳性表达率逐渐升高(P<0.05);宫颈癌组织中TRAIL阳性表达率明显低于宫颈CIN和慢性宫颈炎组织(P<0.05);MEKK3阳性表达率在宫颈癌FIGO分期、浸润深度及淋巴结是否转移阳性率分别递增(均P<0.05),而与患者年龄、组织学类型及分级无关(均P>0.05);TRAIL阳性表达率与宫颈癌组织学分级有关(P<0.05),而与患者年龄、组织学类型、FIGO分期、浸润深度及淋巴结是否转移无关(均P>0.05);MEKK3和TRAIL表达呈负相关(P<0.05);Log-rank分析结果提示MEKK3表达与生存有关(P<0.05),而TRAIL表达与生存无关(P>0.05)。结论 MEKK3和TRAIL异常表达共同参与宫颈癌的发生发展过程,其阳性表达可作为宫颈癌早期诊断及评估生物学行为的分子标志物,MEKK3过表达预示宫颈癌患者不良预后。
Objective To investigate the expression and correlation of mitogen-activated protein kinase kinase (MEKK3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cervical lesions and to analyze its relationship with the clinicopathological features and prognosis of cervical cancer . Methods The chip of cervical lesions was constructed by tissue microarray technique. The expression of MEKK3 and TRAIL in 107 cases of cervical cancer, 86 cases of cervical intraepithelial neoplasia (CIN) and 35 cases of chronic cervicitis were detected by immunohistochemistry En Vision method. At the same time, 44 patients with cervical cancer over the age of more than a year, for survival analysis. Results The positive expression rate of MEKK3 in chronic cervicitis, cervical CIN and cervical cancer tissues was gradually increased (P <0.05). The positive rate of TRAIL in cervical cancer was significantly lower than that in cervical CIN and chronic cervicitis (P <0.05). The positive rate of MEKK3 in FIGO staging, depth of invasion and lymph node metastasis were all increased (all P <0.05), but not with the age, histological type and grade of cervical cancer (all P> 0.05). The positive rate of TRAIL (P <0.05), but not with age, histological type, FIGO stage, depth of invasion and lymph node metastasis (all P> 0.05). There was a negative correlation between the expression of MEKK3 and TRAIL (P <0.05) ; Log-rank analysis indicated that MEKK3 expression correlated with survival (P <0.05), while TRAIL expression had no correlation with survival (P> 0.05). Conclusions The abnormal expression of MEKK3 and TRAIL are involved in the occurrence and development of cervical cancer. The positive expression of MEKK3 and TRAIL may serve as molecular markers for the early diagnosis and assessment of biological behavior of cervical cancer. The overexpression of MEKK3 indicates the prognosis of cervical cancer.