上皮性卵巢癌转移模式相关分子初探

The study of molecular markers associated with clinical classification of epithelial ovarian cancer

目的:筛选和比较不同临床分型(淋巴结转移型/腹膜转移型/混合型)的III期卵巢癌原发灶中的差异表达分子,为晚期卵巢癌的分子分型提供参考。方法:用Tumor Metastasis PCR Array检测淋巴结转移型与腹膜转移型肿瘤组织中肿瘤转移相关分子mRNA表达,Western blot、免疫组化法在肿瘤组织及石蜡包埋组织切片中进一步验证PCR array法筛选出的差异表达分子在蛋白水平的差异表达情况。结果:Tumor Metastasis PCR array筛选出差异表达分子共14个,挑选文献报道的与其它肿瘤淋巴结转移和(或)腹膜转移相关的SMAD4、CCL7、CDKN2A及SERPINE1 4个分子。Western blot结果示,p16(CDKN2A)、CCL7及PAI-1(SERPINE1)在淋巴结转移型原发灶组织中的蛋白表达水平均显著高于腹膜转移型组织。免疫组化结果显示,72例III期上皮性卵巢癌的石蜡包埋组织中,PAI-1蛋白表达水平在淋巴结转移组、腹膜转移组及混合组之间有显著差异,平均评分分别为10.7、7.28及8.13分(P=0.036)。结论:PAI-1表达水平在不同转移模式的IIIc期卵巢癌中存在显著差异,在淋巴结转移型组织中最高,其次为混合型,腹膜转移型最低,可考虑作为卵巢癌分型的潜在分子标记物。

Objective： Screening different moleculars in tumor tissue from patients with ovarian cancer who presented peritoneal dissemination and/or lymph node metastasis.Methods：Detecting different moleculars in tumor tissue from ovarian cancer patients（ 5 patients in the lymph node metastasis group while 4 patients in the peritoneal metastasis group） with human tumor metastasis PCR array.Then confirming the identified moleculars in tumor tissue with western blot.Finally,confirming the moleculars in paraffin-embedded ovarian cancer tissue with immunohistochemistry assay. Results： Fourteen molecules were found to be significantly different for mRNA between the two groups. SMAD4,CCL7,CDKN2 A and SERPINE1 were chosen according to the published reports in ovarian cancer and other malignancies for further study for they had been reported to be correlated with either lymph node metastasis or peritoneal metastasis in other malignancies.In the grey level difference analysis of Western blot,CCL7,CDKN2 A（ P16 INK4 a） and SERPINE1 showed higher level of protein expression in specimens of Group I than Group II（ P〈0.05）.In IHC assay,analysis indicated that only PAI-1 protein showed significant different expression levels in lymph node metastasis group,peritoneal dissemination group and mixed group,the average score were 10.7,7.28 and 8.13 respetively（ P = 0.036）. Conclusion： PAI-1 protein may be one of the moleculars with different expression level in epithelial ovarian cancer with different metastasis modes,and it is expected to become a marker for molecular classification of ovarian cancer.