EGFR和自噬相关蛋白Atg5、p62在宫颈癌中的表达及意义研究

Expression and clinical significance of EGFR and autophagy-related proteins Atg5 and p62 in cervical cancer

目的分析表皮生长因子受体(Epidermal growth factor receptor,EGFR)和自噬相关蛋白Atg5、p62在宫颈癌患者中的表达,探讨其与临床病理及预后因素的关系。方法收集2014年6月至2018年2月收治的80例经病理学证实为宫颈癌患者的组织标本及其癌旁正常组织标本,同时收集上述患者伴有盆腔淋巴结转移组织标本45例。比较宫颈癌组织、转移淋巴结组织和正常组织中EGFR、Atg5、p62表达情况和以上指标与宫颈癌患者临床病理特征及生存情况的关系。结果EGFR、p62在宫颈癌组织转移淋巴结组织中表达率均明显高于癌旁正常组织(P<0.05),Atg5在宫颈癌组织中和转移淋巴结组织中表达率分别为21.25%、33.33%,明显低于正常组织(P<0.05)。EGFR表达阳性率与宫颈癌临床病理参数均无相关性(P>0.05)。Atg5、p62在不同年龄及肿瘤直径中的表达差异无统计学意义(P>0.05),p62表达随肿瘤分化程度升高而降低,不同分化程度间差异有统计学意义(P<0.05),Atg5在不同肿瘤分化程度间差异无统计学意义(P>0.05)。Ⅲ+Ⅳ期和有淋巴结转移患者中的Atg5表达分别低于Ⅰ+Ⅱ期组和无淋巴转移组(P<0.05),而p62的表达与之相反。Spearman相关分析显示,宫颈癌组织中Atg5和p62的表达呈明显负相关(r=-0.656,P<0.01),EGFR与Atg5和p62无相关性(P>0.05);在转移淋巴结组织中,Atg5和p62的表达呈负相关(r=-0.562,P<0.01),EGFR与Atg5和p62无明显相关性(P>0.05)。80例患者随访3年死亡22例,3年生存率为72.50%(58/80),宫颈癌组织中EGFR及p62高表达者3年生存率分别低于EGFR及p62低表达者,而Atg5高表达者3年生存率高于低表达者(P<0.05)。Cox比例风险模型分析显示:TNM分期、淋巴结转移、EGFR、p62为宫颈癌预后的独立危险因素,Atg5为保护因素。结论EGFR、p62在宫颈癌组织及淋巴结转移组织中呈高表达,而Atg5呈低表达,三者可作为宫颈癌患者预后独立预测因素,此外,Atg5及p62与宫颈癌生物学行为有关,可能成为宫颈癌诊断的潜在指标。

Objective To investigate the expressions of epidermal growth factor receptor(EGFR)and autophagy-related proteins Atg5 and p62 in patients with cervical cancer,and to explore its correlation between clinicopathological characteristics and prognostic factors.Methods Eighty cancer tissue specimens and paracancerous tissue in 45 patients with cervical cancer,who were treated in our hospital from June 2014 to February 2018,were collected,at the same time,the 45 specimens of patients with cervical cancer complicated by pelvic cavity lymph node metastasis were collected.The expression levels of EGFR,Atg5 and p62 in cervical carcinoma tissues,metastatic lymph node tissues and normal tissues as well as their correlation with clinicopathological features and survival rate were observed and compared.Results The expression rates of EGFR and p62 in cervical carcinoma tissues and metastatic lymph node tissues were significantly higher than those in paracancerous tissues(P<0.05),while the expression rates of Atg5 in cervical carcinoma tissues and metastatic lymph node tissues(21.25%,33.33%)were significantly lower than those in normal tissues(P<0.05).There was no significant correlation between the positive rate of EGFR expression and the clinicopathological parameters of cervical cancer(P>0.05).The expressions of Atg5 and p62 in different ages and tumor diameters were not statistically significant(P>0.05).The expression of p62 changed with that of the degree of tumor differentiation.There were significant differences in differentiation degree(P<0.05),however,there were no significant differences in the expression of Atg5 in differentiation degrees(P>0.05).Moreover,the expression levels of Atg5 duringⅢ+Ⅳperiod in patients with lymph node metastasis were significantly lower than those duringⅠ+Ⅱperiod and those without lymph node metastasis(P<0.05),but the expression levels of p62 was duringⅢ+Ⅳperiod in patients with lymph node metastasis were significantly higher than those duringⅠ+Ⅱperiod and those without lymph node metastasis(P<0.05).Spearman correlation analysis showed that there was a negative correlation between Atg5 and p62 expression in thyroid cancer tissues(P<0.01),and there was no significant correlation between EGFR and Atg5 as well as(P>0.05).Among the 80 cases,22 cases died after 3-year follow-up,with the survival rate being 72.50%(58/80).The 3-year survival rates in patients with higher expression of EGFR and P62 were significantly lower than those of patients with lower expression of EGFR and P62(P<0.05).And the 3-year survival rates in patients with higher expression of Atg5 were significantly higher than those of patients with lower expression of Atg5(P<0.05).In addition,Cox proportional risk model analysis showed that TNM stage,lymph node metastasis,EGFR and p62 were independent risk factors for the prognosis of patients with cervical cancer,however,the Atg5 was the protective factor.Conclusion GFR and p62 are highly expressed in cervical cancer tissues and lymph node metastasis tissues,however,Atg5 is lowly expressed.The three indexes can be regarded as independent predictors for the prognosis of patients with cervical cancer.In addition,Atg5 and p62 are related with the biological behavior of the patients with cervical cancer,which can be used as potential indicators of prognosis of patients.