宫颈鳞癌组织中KAI1表达变化与宫颈癌复发及预后的相关性研究

Protein and mRNA expression of KAI1 metastasis suppressor gene and its clinical significance in cervical carcinoma

目的:检测宫颈鳞癌肿瘤抑制基因1(KAI1)蛋白和mRNA的表达,结合临床病理资料探讨其与宫颈癌侵袭转移及复发和预后的关系。方法:样本包括正常对照宫颈组织20例,宫颈上皮内瘤变(CIN)组织20例,宫颈癌组织40例。采用免疫组织化学法检测3组间石蜡切片KAI1蛋白表达,采用反转录-多聚酶链反应(RT-PCR)方法检测对照组与宫颈癌组新鲜组织KAI1mRNA的表达。统计相关临床资料并随访其复发及预后情况,采用Cox比例风险模型及Logistic回归分析其与复发与预后的关系。结果:KAI1在正常宫颈组织、CIN及宫颈癌中基因及蛋白表达阳性率均呈进行性下降,组间比较差异显著(P<0.01)。KAI1基因及蛋白表达均与宫颈鳞癌组织分化程度及淋巴转移有关,高分化组较低分化组阳性表达率显著降低(P<0.01),未转移组中的阳性率显著高于淋巴转移组(P<0.05)。宫颈癌按临床分期不同期别越早蛋白表达率越高(P<0.05),基因表达率与临床期别无关。生存分析及Logistic回归分析显示组织学类型差,临床分期晚,有淋巴结转移及KAI1蛋白与RNA表达阳性患者具有高复发风险。临床分期、淋巴结转移及KAI1蛋白与RNA表达与否均为预后相关因素。结论:KAI1基因及蛋白表达强度与宫颈癌组织分化、临床分期及转移均有关,基因表达基本与蛋白表达同步变化,提示KAI1变化可能参与了宫颈癌发生发展,并且是宫颈癌复发与预后的相关因素。

AIM： To study the mRNA and protein expression of Kang ai1 （KAI1） tumor suppressor gene and to determine the relationship between KAI1 and invasiveness and metastasis of cervical cancer. METHODS： The expression of KAI1 metastasis suppressor was detected by immunohistochemistry in paraffin slides and by real-time quantitative polymerase chain reaction （RT-PCR） in fresh tissue. The samples included 20 cases of normal cervical tissues, 20 cases of cervical intraepithelial neoplasia （CIN） and 40 cases of cervical carcinoma. The results of the gene expression combined with the pathological and clinical data were also analyzed. RESULTS： The expression of KAI1 protein and mRNA was related to the tissue differentiation of cervix. The positive rates of KAI1 expression were the highest in the normal cervical tissue, the middle in CIN and the lowest in cervical carcinoma with significant difference among three groups （P〈0.01）. The expression of KAI1 protein was not related with the grade of CIN （P〉0.05）. However, both mRNA and protein expression of KAI1 were related to the differentiation and the clinical stages of cervical cancer （P〈0.01） and also related to the metastasis of the cancer. The positive rates between the non-lymphatic metastasis and lymphatic metastasis （P〈0.05） were significant different. Cox regression and logistic regression showed that the tissue differentiation, clinical stages, lymphatic metastasis and expression of KAI1 were all related factors with recurrence and prognosis of cervical cancer. CONCLUSION： The down-regulation of KAI1 tumor suppressor gene at both mRNA and protein levels is related to the differentiation, clinical stages and metastasis of cervical cancer, indicating that the expression of KAI1 is a prognostic factor for cervical cancer.