【作者】 王晓；

【导师】 王焱；

【作者基本信息】 河南科技大学 ， 临床医学硕士（专业学位）， 2019， 硕士

【摘要】 目的:通过观察PAK家族与Spred在不同宫颈组织中的表达及各组织中HPV的感染情况,探讨PAK家族、Spred、HPV感染与宫颈病变发生、发展的关系及其相互之间的相关性。方法:收集2015年10月至2017年12月河南科技大学第一附属医院行手术及活检的宫颈组织标本共154例,年龄在24~68岁,中位年龄50岁;其中正常组标本(均为因非宫颈疾病行全子宫切除术的正常宫颈组织)40例,中位年龄49岁;LSIL组标本24例,HSIL组标本31例,中位年龄43岁;宫颈鳞癌标本(标本均已经过组织病理检查证实,腺癌已除外,标本仅纳入鳞癌标本)59例,中位年龄55岁。根据不同病理特征对宫颈鳞癌进行分组:按照年龄:其中<55岁21例,≥55岁38例;按照临床分期(FIGO,2009年)其中Ⅰ-ⅡA期48例、ⅡB-Ⅳ期11例;按照分化程度:高分化22例、中-低分化37例;根据有无淋巴结转移:无淋巴结转移19例、有淋巴结转移29例。实验标本纳入标准为:(1)术前3月内未接收药物治疗;(2)术前均未接受新辅助化疗、放疗和中药治疗,未服用保健产品;(3)临床病理资料完整、病例信息完整者。实验所纳入标本术前均行HPV-DNA分型检测,应用免疫组化S-P法检测154例宫颈组织标本中PAK和Spred的表达情况,分析PAK、Spred、HPV感染与宫颈鳞癌关系及其相互之间的相关性。结果:1.PAK家族中,PAK1在正常组、LSIL组、HSIL组、宫颈鳞癌组中阳性率逐渐升高,PAK6在各组中的阳性率也随宫颈病变程度的加重而升高;而Spred的阳性率随宫颈病变程度加重则逐渐降低。2.在宫颈鳞癌组织中,PAK家族:PAK1的表达与病理分级、有无淋巴转移有关(均有P<0.05),与年龄及临床分期无关(均P>0.05);PAK6的表达与病理分级、有无淋巴是否转移有关(均P<0.05),与年龄及临床分期无关(均P>0.05),由此可知:分化程度低、有淋巴转移者PAK的阳性表达率越高,反之阳性率越低。Spred的表达仅与病理分级有关(P<0.05),与年龄及临床分期、有无淋巴结转移均无关(均P>0.05),分化程度越高Spred的阳性表达越高,反之阳性率越低。3.HPV-DNA感染的阳性率随宫颈病变程度的加重而逐渐升高,且各组间差异具有统计学意义(P<0.05)。4.在不同宫颈组织中PAK1的表达与Spred的表达呈负相关性(P<0.01);PAK6与Spred呈负相关(P<0.01);PAK1与PAK6呈正相关(P<0.01)。5.在各组中,PAK1的阳性表达与HPV感染呈正相关(P<0.01);PAK6的阳性表达与HPV感染呈正相关(P<0.01);Spred的阳性表达与HPV感染呈负相关(P<0.01)。结论:1.PAK家族:PAK1和PAK6在不同宫颈组织中表达的阳性率均随宫颈病变程度的加重而升高;Spred表达的阳性率随着宫颈病变程度的加重而降低,两者呈负相关性。2.在宫颈鳞癌组,PAK家族:PAK1、PAK6的阳性表达均与病理分级和有无淋巴转移有关;Spred的阳性表达仅与病理分级有关;提示PAK家族可能参与宫颈病变的进展,并且与宫颈鳞癌的恶性程度、转移及预后有关;Spred可能与宫颈病变的进展及宫颈鳞癌的恶性程度有关。3.PAK家族及Spred可能参与了HPV感染相关的宫颈鳞癌的发病及进展。更多还原

【Abstract】 Objective:By observing the expression of PAK family and Spred and the infection of HPV in different cervical tissues,to investigate the relationship between PAK family,spred,HPV infection and the occurrence of cervical lesions.Methods:A total of 154 specimens of cervical tissue from the first affiliated Hospital of Henan University of Science and Technology were collected from October 2015 to December 2017,aged 24 years and 68 years,with a median age of 50 years.The normal group(n=40),all of them underwent total hysterectomy due to non-cervical diseases,with a median age of 49 years.The LSIL group(n=24)and the HSIL group(n=31),whose of the median age was 43 years old.The squamous carcinoma of the cervix group have been confirmed by histopathological examination(n=59),whose of the median age was 55 years old.Cervical squamous cell carcinoma specimens were grouped according to different pathological characteristics.According to the age of the patient,it can be divided into <55 yeaes(n=24)and ≥55 yeaes(n=24).According to clinical staging(FIGO,2009),it can be divided into Ⅰ-Ⅱ A(n = 48)and ⅡB-Ⅳ(n=1).According to the degree of differentiation,it can be divided into high differentiation(n=22)and moderate-low differentiation(n=37).According to the presence or absence of lymph node metastasis,it can be divided into non-lymphatic metastasis(n=19)and lymphatic metastasis(n = 29).The inclusion criteria for experimental specimens are as follows:(1)No drug treatment was received within 3months before operation.(2)None received neoadjuvant chemotherapy,radiotherapy and traditional Chinese medicine before the operation,and one health products.(3)Complete clinicopathological data and case information.All specimens were detected by HPV-DNA typing before operation.Immunohistochemical method was used to detect the expression of PAK and Spred in cervical tissue samples.And analyzing the relationship between PAK,Spred and HPV infection and cervical squamous cell carcinoma and the correlation between them.Results:1.The positive rate of PAK1 increased gradually in normal group,LSIL group,HSIL group and cervical squamous cell carcinoma group.The positive rate of PAK6 ineach group also increased with the severity of cervical lesions.Howeber the positive rate of spred decreased with the severity of cervical lesions.2.In cervical squamous cell carcinoma,PAK family,which include PAK1 and PAK6,whose positive expression are related to pathological grade,lymph node metastasis or not(P<0.05),not related to age or clinical staging(P>0.05).That is to say,the lower the differentiation degree,the higher the positive expression rate of PAK in the group of low differentiation and lymph node metastasis,and on the contrary,the lower the positive rate.The expression of Spred is only related to pathological grade(P<0.05),but not with age,clinical stage and lymph node metastasis(P>0.05).The higher the degree of differentiation,the higher the positive expression of spred,and vice versa,the lower the positive rate,otherwise the lower the positive rate.3.The positive rate of HPV-DNA infection increased with the severity of cervical lesions,the differences among the groups were statistically significant(P<0.05).4.There was a negative correlation between the expression of PAK1 and Spred(P<0.01),PAK6 and Spred(P<0.01),but a positive correlation between PAK1 and PAK6(P<0.01)in different cervical tissues.5.In each group,the positive expression of PAK1 was positively correlated with the infection of HPV(P<0.01),and the positive expression of PAK6 was positively correlated with the infection of HPV(P<0.01).The positive expression of spred was negatively correlated with hpv infection(P<0.01).Conclusions:1.PAK1 and PAK6,members of the pak family,whose positive rate of their expression increased with the severity of cervical lesions in different cervical tissues,while the positive rate of the expression of spred decreases with the severity of the cervical lesion.There was a negative correlation between them.2.In cervical squamous cell carcinoma,PAK1 and PAK6,members of the pak family,whose positive expression was related to the pathological grade and lymph node metastasis,and the positive expression of spred was only related to the pathological grade.It is suggested that the PAK family may be involved in the progression of cervical lesions,and may be related to the malignant degree,metastasis and prognosis of cervical squamous cell carcinoma,and spred may be related to the progression of cervical lesions and the malignant degree of cervical squamous cellcarcinoma.3.PAK family and Spred may be involved in the pathogenesis and progression of cervical squamous cell carcinoma associated with HPV infection.更多还原