Beclin1、EGFR、cyclinD1在新辅助化疗宫颈癌组织中的表达及临床意义

目的研究自噬标记蛋白Beclin1、表皮生长因子受体(EGFR)、细胞周期蛋白D1(cyclinD1)在新辅助化疗宫颈癌组织中的表达及意义。方法收集2015年3月至2018年2月医院收治的局部晚期宫颈癌80例,术前接受卡铂联合紫杉醇新辅助化疗3个周期,新辅助化疗前后均留取宫颈癌组织标本,并选取行子宫切除的20例患者的正常宫颈上皮组织作为对照组,免疫组化法测定新辅助化疗前后宫颈癌组织Beclin1、EGFR、cyclinD1表达的变化,与正常宫颈上皮组织进行对照,比较不同疗效宫颈癌患者组织Beclin1、EGFR、cyclinD1表达及临床病理资料的差异,多因素Logistic回归分析法筛选宫颈癌新辅助化疗疗效影响因素。结果宫颈癌化疗前后组织Beclin1阳性率低于对照组,EGFR、cyclinD1阳性率高于对照组(P<0.05),化疗后癌组织Beclin1阳性率高于化疗前,EGFR、cyclinD1阳性率低于化疗前(P<0.05);80例患者新辅助化疗3个周期有效55例(68.75%),无效25例(31.25%),有效组癌组织Beclin1阳性率高于无效组,EGFR、cyclinD1阳性率低于无效组(P<0.05);无效组临床分期为Ⅱa1~b1期、组织分化程度为低中分化、伴淋巴结转移所占比例高于有效组(P<0.05);Beclin1、EGFR、cyclinD1、组织分化程度、淋巴结转移均为宫颈癌新辅助化疗疗效影响因素(P<0.05)。结论宫颈癌癌组织EGFR、cyclinD1呈异常高表达,Beclin1呈低表达,新辅助化疗可降低EGFR、cyclinD1阳性率,提升Beclin1阳性率,促成宫颈癌自噬网建立,诱导癌细胞凋亡;Beclin1、EGFR、cyclinD1、组织分化程度、淋巴结转移均为影响宫颈癌新辅助化疗效果的因子。

The Expressions and Clinical Significances of Beclin1,EGFR and CyclinD1 in Cervical Cancer Tissues Undergoing Neoadjuvant Chemotherapy

Objective To study the expressions and significances of autophagy marker protein Beclin1,epidermal growth factor receptor(EGFR)and cyclin D1 in cervical cancer tissues undergoing neoadjuvant chemotherapy.Methods Eighty patients with locally advanced cervical cancer who were admitted to the hospital from March,2015 to February,2018 were selected for the study.They underwent 3 cycles of carboplatin and paclitaxel neoadjuvant chemotherapy before surgery,and cervical cancer tissue specimens were collected before and after neoadjuvant chemotherapy.Normal cervical epithelial tissues of 20 patients undergoing hysterectomy were collected as the control group.Changes in expressions of Beclin1,EGFR and cyclin D1 in cervical cancer tissues were determined by immunohistochemistry before and after neoadjuvant chemotherapy.With normal cervical epithelial tissues as controls,the expressions of Beclin1,EGFR and cyclinD1 and related clinical pathological data were compared among patients with different therapeutic effects.Multivariate logistic regression analysis was performed to screen factors influencing the curative effect of neoadjuvant chemotherapy for cervical cancer.Results The positive rates of Beclin1 in cervical cancer before and after chemotherapy were lower than those in the control group.The positive rates of EGFR and cyclinD1 were higher than the control group(P<0.05).The positive rate of Beclin1 in cancer tissues was higher than that of before chemotherapy.The positive rates of EGFR and cyclinD1 were lower than those of before chemotherapy(P<0.05).Among the 80 patients undergoing 3 cycles of neoadjuvant chemotherapy,the chemotherapy was effective in 55 cases(68.75%)and ineffective in 25 cases(31.25%).The positive rate of Beclin1 in the effective group was higher than that in the ineffective group,and the positive rates of EGFR and cyclinD1 were lower than those in the ineffective group(P<0.05).The proportions of clinical stage of IIa1-b1,low and middle differentiation and lymph node metastasis in the ineffective group were lower than those in the effective group(P<0.05).Beclin1,EGFR,cyclinD1,tissue differentiation degree and lymph node metastasis were all factors affecting the curative effect of neoadjuvant chemotherapy for cervical cancer(P<0.05).Conclusion The expressions of EGFR and cyclinD1 are abnormally high and the expression of Beclin1 is low in cervical cancer tissues.Neoadjuvant chemotherapy can decrease the positive rates of EGFR and cyclinD1,increase the positive rate of Beclin1,promote the establishment of autophagy network of cervical cancer,also induce apoptosis of cancer cells.Beclin1,EGFR,cyclinD1,tissue differentiation and lymph node metastasis are all factors that influence the effects of neoadjuvant chemotherapy for cervical cancer.