HPV感染宫颈癌患者Hippo-YAP通路改变及其与临床特征的关系

Correlation between change of Hippo-YAP pathway in cervical cancer patients with HPV infection and clinical characteristics

目的探讨人乳头瘤病毒(HPV)感染宫颈癌患者Hippo-YAP信号通路yes相关蛋白1(YAP1)在宫颈组织中的YAP1 mRNA和蛋白表达及其与临床特征的相关性。方法选择湖北省中西医结合医院妇产科2015年1月-2020年5月收治的宫颈癌患者85例作为研究组,选择同期医院收治的宫颈上皮内瘤变(CIN)患者40例作为CIN组及因子宫良性病变进行子宫切除术患者60例作为对照组;采用实时荧光定量聚合酶链式反应(RT-PCR)检测YAP1 mRNA表达,采用免疫组化法检测宫颈组织中YAP1免疫组化评分;比较宫颈癌患者不同临床参数YAP1 mRNA、YAP1免疫组化评分差异;比较YAP1不同mRNA水平、免疫组化评分患者无病生存期、总生存期。结果宫颈癌组YAP1 mRNA表达、YAP1免疫组化评分均高于CIN组及对照组(P<0.05);CIN组YAP1 mRNA表达、YAP1免疫组化评分高于对照组(P<0.05);宫颈组织中YAP1 mRNA表达、YAP1免疫组化评分与患者淋巴结转移有关(P<0.05),与其他临床参数无关;以各自平均值作为区分界限,YAP1 mRNA高表达、YAP1免疫组化高评分患者无病生存期、总生存期缩短(P<0.05)。结论宫颈癌组织中YAP1 mRNA、蛋白表达明显升高,且与肿瘤转移存在联系,可作为患者预后指标,其内在机制有待进一步探讨。

OBJECTIVE To investigate the correlation between the expression of Hippo-YAP signaling pathway genes and proteins in cervical tissues and clinical pathological characteristics of the cervical cancer patients with human papilloma virus(HPV)infection.METHODS Totally 85 patients with cervical cancer who were treated in the department of obstetrics and gynecology of Hubei Provincial Hospital of Integrated Chinese and Western Medicine from Jan 2015 to May 2020 were assigned as the study group,meanwhile,40 patients with cervical intraepithelial neoplasia(CIN)were assigned as CIN group,60 patients with benign lesions of uterus who underwent hysterectomy were set as the control group.The relative expression level of YAP1 on mRNA was detected by using real-time fluorescent quantitative polymerase chain reaction(RT-PCR),the YAP1 in cervical tissue was detected by means of immunohistochemistry,and the immunohistochemical score was calculated;the differences in YAP1 mRNA and YAP1 immunohistochemical scores of the patients with cervical cancer were compared;the disease-free survival and overall survival were compared among the patients with different YAP1 mRNA levels and immunohistochemical scores.RESULTS The relative expression level of YAP 1 gene on mRNA and YAP1 immunohistochemical score were significantly higher in the cervical cancer group than in the CIN group and the control group(P<0.05);the relative expression level of YAP 1 gene on mRNA and YAP1 immunohistochemical score were significantly higher in the CIN group than in the control group(P<0.05).The relative expression of YAP1 gene on mRNA and YAP1 immunohistochemical score were significantly associated with the lymph node metastasis(P<0.05)and were not associated with other clinical parameters.Taken the respective average values as the distinguishing limit,the disease-free survival and overall survival of the patients with high relative expression of YAP 1 gene mRNA and high YAP1 immunohistochemical score were significantly shorter(P<0.05).CONCLUSION The expression of YAP1 mRNA and proteins in cervical cancer tissues is significantly increased,which is associated with tumor metastasis,and it can be used as an indicator for prediction of prognosis.The internal mechanisms needs to be further explored.