子宫颈鳞状细胞癌中SIAH2蛋白表达的临床意义

Clinical value of SIAH2 expression in cervical squamous cell carcinoma

目的探讨SIAH2表达与子宫颈鳞状细胞癌临床病理特征和患者预后的关系。方法采用免疫组化法检测癌旁正常子宫颈组织、高级别鳞状上皮内病变及子宫颈鳞状细胞癌组织中SIAH2的表达,统计分析SIAH2与子宫颈鳞状细胞癌临床病理特征的关系。应用RT-qPCR和Western blot法检测子宫颈新鲜组织中SIAH2 mRNA和蛋白的表达。利用Kaplan-Meier法绘制生存曲线,单因素和多因素分析比较组间临床病理特征及评估患者预后因素。结果免疫组化结果表明,癌旁正常子宫颈(5.00%)、高级别鳞状上皮内病变(48.33%)和子宫颈鳞状细胞癌(75.83%)中SIAH2的阳性率逐渐升高(P<0.05)。SIAH2表达与子宫颈鳞状细胞癌FIGO分期、淋巴结转移、高危HPV16感染和Ki-67表达相关(P均<0.05)。Spearman相关性分析显示,子宫颈鳞状细胞癌中SIAH2表达与高危HPV16感染和Ki-67表达呈正相关(P均<0.05)。RT-qPCR和Western blot结果显示,子宫颈鳞状细胞癌中SIAH2 mRNA和蛋白的相对表达量显著高于癌旁正常子宫颈组织(P<0.05)。生存分析发现,SIAH2阳性子宫颈鳞状细胞癌患者的生存时间明显短于阴性者(P<0.05)。Cox多因素回归分析结果表明,SIAH2高表达是子宫颈鳞状细胞癌患者总生存期的独立预测因子。结论SIAH2可能作为一个癌基因参与子宫颈鳞状细胞癌的发展和转移,其过表达提示患者预后不良;SIAH2有望成为子宫颈鳞状细胞癌靶向治疗和预后评估的指标之一。

Purpose To investigate the relationship between the expression of Seven-In-Absentia Homolog 2(SIAH2)and clinicopathological parameters and prognosis of cervical squamous cell carcinoma(CSCC)patients.Methods Immunohistochemical staining was used to detect the expression of SIAH2 in neighboring noncancerous cervix,high-grade squamous intraepithelial lesion(HSIL)and CSCC,and the relationship between SIAH2 protein and clinicopathologic factors of CSCC was analyzed.And in fresh specimens by RT-qPCR and Western blot were used.In combination with follow-up data,survival curves were calculated using the Kaplan-Meier method.Clinicopathological characteristics were compared and prognostic factors were evaluated using univariate and multivariate analyses.Results The immunohistochemistry results showed there was an increasing tendency in positive rate of SIAH2 expression from neighboring noncancerous cervix(5.00%)to HSIL(48.33%)to CSCC(75.83%),and the difference was statistically significant(P<0.05).The expression of SIAH2 was correlated with FIGO stage,lymphatic metastasis,HR-HPV16 infection and Ki-67 expression(all P<0.05).The Spearman’s correlation test revealed that the SIAH2 expression was significantly positively associated with HR-HPV16 infection and Ki-67 expression in CSCC specimens(both P<0.05).The relative expression of SIAH2 mRNA and protein in CSCC was significantly higher thanthat in the neighboring noncancerous tissue,and there was significant difference(P<0.05).Survival analysis revealed a shorter overall survival in CSCC patients with SIAH2 expression(P<0.05).The multiple factor analysis revealed that the higher expression of SIAH2 was independent prognostic factor for overall survival.Conclusion SIAH2 may be involved in the development and metastasis of CSCC as an oncogene,and the overexpression of SIAH2 indicated poor prognosis of the disease,a finding which might be helpful for the treatment and prognosis of CSCC patients.