乳腺癌组织乙酰肝素酶表达临床意义Meta分析

Meta-analysis of heparanase expression in breast cancer and the clinical significance

目的乙酰肝素酶（heparanase,HPSE）被认为与乳腺癌细胞的生长和转移能力相关。本研究系统评价HPSE在不同乳腺癌组织中的表达,探讨其临床意义。方法检索Pubmed、Medline via OvidSP,CBM、CNKI、VIP和WanFang等数据库至2015-04-30,并手动检索相关文献。评价指标为乳腺癌组织与正常组织（或癌旁组织）中HPSE表达的差异;不同侵袭转移类型的乳腺癌组织中HPSE表达差异;HPSE与淋巴结转移、患者生存率及雌激素受体（estrogen receptor,ER）的相关性。采用纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale,NOS）对纳入的文献进行质量评价,RevMan5.3软件进行数据分析。结果最终纳入16个研究,1 540例样本。Meta分析结果显示,与正常乳腺组织和癌旁组织相比,乳腺癌组织中HPSE表达显著增高,OR=47.33,95%CI为3.56～629.16,P=0.003;OR=32.75,95%CI为10.43～102.83,P〈0.001。浸润性乳腺癌组织中HPSE表达显著高于非浸润性乳腺癌组织,OR=6.30,95%CI为3.16～12.58,P〈0.001。淋巴结转移阳性组中HPSE表达显著高于淋巴结转移阴性组,OR=4.94,95%CI为3.39～7.18,P〈0.001。HPSE阴性的患者5年内的预后优于阳性组,OR=0.23,95%CI为0.12～0.47,P〈0.001。ER阳性组中HPSE表达高于ER阴性组,但差异无统计学意义,OR=1.77,95%CI为0.79～3.96,P=0.06。结论基于目前的临床数据显示,与正常乳腺组织和癌旁组织相比,乳腺癌组织中HPSE呈现过表达,且浸润性乳腺癌HPSE表达增加,高表达的HPSE与淋巴结的转移阳性和5年内不良预后相关,但HPSE和ER相关性需要更多的研究来证实。

OBJECTIVE Heparanase（HPSE）was reported to be related to the proliferation and migration of breast cancer cells,a systematic review was conducted to evaluate the HPSE expression in different breast cancer tissues and determine the clinical significance.METHODS We searched several databases,such as PubMed,MEDLINE via OvidSP,CBM,CNKI,VIP and WanFang（cutoff date：April 30,2015）,and manually retrieved the relevant literature.The considered endpoints included the difference in HPSE expression between breast cancer and normal tissue（or adjacent tissue）,the difference in HPSE expression between breast cancer subtypes with different invasive and metastatic ability,and the relationship between HPSE expression and lymph node metastasis,survival rate and estrogen receptor（ER）status.Methodogical quality was assessed using Newcastle-Ottawa Scale（NOS）.Revman 5.3was applied for data analysis.RESULTS A total of 16 studies and 1 540 samples were included in this meta-analysis,and it was found that HPSE expression was significantly higher in breast cancer tissue compared with normal breast tissue and adjacent tissue（OR=47.33,95%CI=3.56-629.16,P=0.003;OR=32.75,95%CI=10.43-102.83,P〈0.001）.Moreover,HPSE expression was significantly higher in breast cancer with high ability of invasive and metastatic（OR=6.30,95%CI=3.16-12.58,P〈0.001）.There were significantly more HPSE-positive cases in the group with lymph node metastasis than the group without lymph node metastasis（OR=4.94,95%CI=3.39-7.18,P〈0.001）.The HPSE-negative patients had a better5-year prognosis than that of HPSE-positive patients（OR=0.23,95%CI=0.12-0.47,P〈0.001）.HPSE expression was higher in the ER-positive group than that in the ER-negative group（OR=1.77,95%CI=0.79-3.96,P=0.06）,but the difference was not significant.CONCLUSIONS Based on the current evidence,the results suggested that HPSE is overexpressed in breast cancer tissue compared with normal or pericarcinomatous breast tissue.HPSE expression is higher in breast cancer with high ability of invasive and metastatic.High HPSE expression is related to lymph node metastasis and worse prognosis,the correlation between ER status and HPSE needs to be further verified by more trials.