HPV16阳性宫颈鳞癌组织EGFR上游与下游相关蛋白表达临床意义探讨  

Clinical significance of the expression of EGFR related upstream and downstream proteins in HPV16-positive cervical squamous cell carcinoma

作　　者：张典刚[1] 刘凯[1] 赵俊玲[1] 古丽娜[1] 李文婷[2] 王若峥[1] 

机构地区：[1]新疆医科大学附属肿瘤医院放疗中心,新疆乌鲁木齐830011 [2]新疆医科大学附属肿瘤医院病理科,新疆乌鲁木齐830011

出　　处：《中华肿瘤防治杂志》2015年第16期1277-1282,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：科技部国际合作项目(2012DFA31560)

摘　　要：目的探讨HPV阳性宫颈鳞癌（cervicalsquamouscellcarcinoma，CSCC）组织中表皮生长因子受体（epidermalgrowthfactorreceptor，EGFR）、Rab5a、Rab21、c-jun、plos蛋白表达关系及临床意义。方法收集2012—09—01—2013-09—30新疆医科大学附属肿瘤医院病理科保存的初治HPV阳性CSCC组织标本45例。其中维吾尔族人群标本33例，汉族人群标本12例，年龄30～70岁，中位年龄46岁。采用免疫组织化学法检测45例HPV阳性CSCC组织中EGFR、Rab5a、Rab21、c-jun和c-los蛋白表达情况。结果EGFR、Rab5a、Rab21、c-jun和c-los蛋白阳性表达率分别为64．4％、66．7％、60．0%、75．6％和66．7％；EGFR蛋白表达与临床分期（x2=8．008，P=0．005）、淋巴结转移（x2=7．162，P=0．007）有关，Rab5a蛋白表达与临床分期（x2=10．045，P=0．002）、肿瘤分化程度（x2=3．906，P=0．048）、淋巴结转移（x2=5．511，P=0．019）有关，Rab21蛋白表达与临床分期（x2=9．644，P=0．002）、淋巴结转移（x2=23．766，PG0．001）有关，c-jun（x2=4．022，P=0．045）、c-fos（x2=18．219，PG0．001）蛋白表达与淋巴结转移有关。Spearman等级相关分析显示，c-jun、c-los蛋白表达与肿瘤分化程度呈负相关（r=-0．347，P=0．020；r=-0．299，P=0．046），与临床分期呈正相关（r=0．362，P=0．015；r=0．329，P=0．028）；EGFR与Rab21表达呈负相关（r=-0．322，P=0．031），EGFR与Rab5a、c-jun、c-los表达呈正相关（r值分别为0．558、0．658和0．755，P值均G0．001）。结论HPV阳性CSCC中Rab21蛋白可能阻碍EGFR介导的信号传导，Rab5a、c-jLln、c-los蛋白可能促进EGFR介导的细胞信号传导，EGFR、c-jun、c-los、Rab21、Rab5a可能作为CSCC发展、转移的参考指标。联合检测EGFR、c-jun、c-fos、Rab5a、Rab21可为CSCC的诊断、寻找新的治疗靶点和预后评估提供依据。OBJECTIVE To discuss the relationship among the expression of EGFR, Rab5a, Rab21, c-jun and c-los and its clinical significance in HPV16-positive cervical squamous cell carcinoma. METHODS Forty-five cases of novo HPV-positive CSCC specimens were collected from 2012-09-01 to 2013-09-30 in Department of Pathology Xinjiang Medi- cal University Cancer Hospital in which 33 cases were from Uighur population and 12 cases were from Han population. Age range was from 30 to 70 years old, with a median age of 46 years. The immunohistochemistry was used to detect EG- FR, Rab5a, Rab21, e-jun and c-fos protein expression in 45 cases of HPV16-positive CSCC tissues. RESULTS EGFR, Rab5a, Rab21, c-jun, c-los protein expression rates were 64.4%, 66.7%, 60.0%, 75.6%, 66.7%, EGFR protein ex- pression was correlated with clinical stage（x2 = 8. 008, P ： 0. 005） and lymph node metastasis （x2 = 7. 162, P = 0. 007）, Rab5a protein expression was correlated with clinical stage（x2= 10. 045, P=0. 002）, tumor differentiation （X2 = 3. 906, P=0. 048） and lymph node metastasis（x2= 5. 511, P=0. 019）, Rab21 protein expression was correlated with clinical stage（x2 =9. 644 ,P=0. 002） and lymph node metastasis（x2 =23. 766 ,P〈0. 001）, c-jun protein expression（x2 = 4. 022, P= 0. 045）and c-fos protein expression （x2 = 18. 219, P〈0. 001）were correlated with lymph node metastasis. Spearman rank correlation analysis showed that c-jun, c-los protein expression were negatively correlated with tumor differentiation （r=-0.347,P=0.020; r=-0.299,P 0.046）, were positively correlated withclinicalstage（r--0.362,P=0.015;r= 0. 329,P=0. 028）, EGFR was negatively correlated with Rab21 expression （r=-0. 322, P=0. 031）, EGFR was posi- tively correlated with Rab5a, c-jun, c-los expression （r=0. 558,P〈0. 001; r=0. 658,P〈0. 001; r=0. 755,P〈0. 001）. CONCLUSIONS Rab21 protein may play a negative role in the regulation of EGFR-mediated signaling pathways. Rab5a, c-jun and c-fos protein may play a positive role in t

关 键 词：宫颈鳞状细胞癌 表皮生长因子受体 RAB5A Rab21 C-JUN c-fos 人乳头状瘤病毒 

分 类 号：R737.33[医药卫生—肿瘤]