组织蛋白酶D在卵巢高级别浆液性腺癌中的表达及其临床意义

Expression and Evaluation of Cathepsin D in High Grade Serous Adenocarcinoma Cancer of Ovarian

目的 探讨组织蛋白酶D在卵巢高级别浆液性腺癌中的表达及其临床意义.方法 1、选取病理诊断明确的卵巢高级别浆液性腺癌共136例入组研究,留取部分手术切除肿瘤组织,以对侧正常输卵管伞端上皮组织作为非癌对照.将癌及对照非癌组织RNA,电泳质检;q-PCR检测组织蛋白酶D在癌及对应癌旁组织中表达水平,分析其表达与各项临床病理参数关系;2、构建组织芯片,运用免疫组化方法分析组织蛋白酶D的蛋白表达水平,分析其与各项临床病理参数关系.结果1、q-PCR检测显示,与非癌组织相比,癌组织中组织蛋白酶D的表达水平显著上调.若以2倍为界值,上调的有99对,下调的仅有8对,另有29对没有变化（P〈0.001）.生存分析显示,肿瘤组织中组织蛋白酶D高表达组的总生存期（OS）显著低于低表达组（P〈0.01）.2、免疫组化分析显示,癌组织中蛋白酶D的阳性表达率为91.9%（125/136）,而在对照非癌组织中,其阳性表达率仅有22.1%（30/136）,差异具有统计学意义（P〈0.01）.同时,其高表达组（3分,76/125）的5年OS显著低于低表达组（0~2分,49/125）,提示不良预后（P〈0.05）.结论 组织蛋白酶D在卵巢高级别浆液性腺癌组织中表达上调,提示其具有潜在＆quot;癌基因＆quot;的作用.并且其表达量与总生存率呈负相关,提示不良预后.

Objective To investigate the expression and clinical significance of cathepsin-D in high-grade serous ovarian cancer. Methods 1.Cancer tissue samples were collected from 136 patients with high-grade serous ovarian cancer verified by pathological examination. Normal fimbria epithelial tissue from the other fallopian tube of the same patient was collected as para-carcinomatous control sample. RNA isolation from cancer and para-carcinomatous normal tissue and RNA integrity assessment by using electrophoresis. Measure cathepsin-D transcriptional activities in cancer tissue and para-carcinomatous normal tissue by q-PCR, then its relationship with clinicopathological parameters investigated. 2.Tissue microarrays were developed, protein levels of cathepsin-D in cancer and para-carcinomatous normal tissue measured by immunohistochemical assay, and the relationship between cathepsin-D protein expression and clinicopathological parameters investigated. Results 1.q-PCR analysis showed cathepsin-D transcriptional activity was significantly upregulated in cancer tissue compared with the normal. Cathepsin-D was increased in cancer tissue of 99 patients, decreased in 8 patients, and kept unchanged in 29 patients （P〈0.01, a twofold difference was considered significant）. The survival analysis indicated the overall survival （OS） was significantly lower in the highly cathepsin-D expressed group （P〈0.01）. 2.Immunohistochemical assay showed cathepsin-D was positively expressed in 91.9% （125/136） of cancer tissue compared with 22.1% （30/136） in para-carcinomatous normal tissue with statistical significance （P〈0.01）. The 5-year overall survival was significantly lower （P〈0.05） in the high cathepsin-D group （score 3, 76/125） than in the low cathepsin-D group （score 0~2, 49/125）, which indicated a high cathepsin-D expression is associated with a poor prognosis. Conclusion Cathepsin-D expression is upregulated in high-grade serous ovarian cancer tissue, which indicates cathepsin-D plays a role of a potential oncoprotein. Cathepsin-D level was inversely associated with overall survival rate. High level of cathepsin-D indicates a poor prognosis.