EphB2和Atg4C在宫颈鳞癌中的表达及其临床意义

Expression and their clinical significance of EphB2 and Atg4C in cervical squamous cell carcinoma

目的:探讨EphB2和Atg4C在宫颈鳞癌中的分布、表达水平及其与患者临床病理参数的关系。方法:随访74例宫颈鳞癌患者并将其肿瘤组织和10例癌旁宫颈组织构建组织芯片。采用量子点免疫荧光组织化学和蛋白印迹技术检测EphB2和Atg4C蛋白在宫颈鳞癌中的表达和分布。结果:免疫组化和蛋白印迹实验均表明EphB2在宫颈鳞癌组织中的表达信号高于癌旁宫颈组织(P=0.036),而Atg4C在宫颈鳞癌组织中的表达信号显著低于癌旁宫颈组织(P=0.042)。在宫颈鳞癌患者中,EphB2的高表达与淋巴结转移(P<0.001)和TNM分期(P=0.002)均显著相关,并可预测患者的不良预后(P=0.003)。Atg4C的低表达与高的TNM分期呈正相关(P=0.002),可预测宫颈鳞癌患者的不良预后(P=0.009)。在宫颈鳞癌中,Atg4C与EphB2的表达水平呈显著负相关性(rs=-0.303;P=0.009),并且,宫颈鳞癌患者肿瘤细胞中高表达EphB2和低表达Atg4C较其他组总体生存最差(P<0.001)。结论:EphB2和Atg4C在宫颈鳞癌中存在异常表达,且Atg4C与EphB2的表达水平存在负相关性,提示自噬可能参与宫颈鳞癌的发生发展。高EphB2和低Atg4C表型是宫颈鳞癌患者总体生存的独立预后因素。

Objective:To investigate the expression,localization and clinical significance of EphB2 and autophagy-related gene 4C(Atg4C)in the human cervical squamous cell carcinoma(SCC)patients′cohort.Methods:Tissue microarrays were constructed from 74 cases of cervical SCC(including 10 samples of non-cancerous cervical tissues as controls)with follow-up data.Quantum dots based immunofluorescence histochemistry and Western blotting were performed to detect the expression levels of Atg4C and EphB2 proteins in cervical SCC tissues.Results:Immunohistochemistry and Western blotting results demonstrated that EphB2 expression was significantly increased in the cancer tissues,compared with noncancerous cervical tissues(P=0.0360),while Atg4C was significantly decreased in the cancer tissues(P=0.0420).High expression of EphB2 protein was associated with lymph node status(P<0.001)and TNM stage(P=0.002),and predicted the poor prognosis of patients with cervical SCC(P=0.003).On the contrary,low expression of Atg4C protein had significant positive correlation with higher TNM stage(P=0.002),and predicted the poor prognosis of patients with cervical SCC(P=0.009).Spearman analysis suggested that Atg4C expression was negatively correlated with the EphB2 expression level(r2=-0.303;P=0.009).In addition,high expression of EphB2and low expression of Atg4C in the cancer cells of patients with cervical SCC predicted the worst prognosis than those in other groups(P<0.001).Conclusion:EphB2 and Atg4C proteins are both dysregulated,moreover,a negative correlation is observed between the expression levels of EphB2 and Atg4C proteins in patients with cervical SCC,which demonstrates that autophagy may involve in the development of cervical SCC.High EphB2 plus low Atg4C phenotype is an independent prognostic factor for the overall survival of patients with cervical SCC.