The association between the prognosis and the localization and expression of heparanase in human laryngeal squamous cell carcinoma
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摘要: 目的:探讨乙酰肝素酶(HPA)在人喉鳞状细胞癌组织中的表达水平与临床分期、T分级、淋巴结转移、病理分化程度等临床病理参数的关系,并分析HPA表达和细胞定位与预后的关系。方法:采用免疫组织化学法检测HPA蛋白在73例喉鳞状细胞癌组织中的表达,分析其与病理特征的关系。Fisher精确检验和卡方检验比较计数资料,Kaplan-Meier生存曲线与Log-rank检验分析生存情况,单因素及多因素COX比例风险回归分析独立预后因子。结果:HPA蛋白在喉鳞状细胞癌组织和对照组息肉组织中的阳性表达率分别为76.71%(56/73)和21.05%(8/38),差异有统计学意义(P<0.05)。HPA的表达水平在不同的临床分期、病理分化、T分级及淋巴结转移之间差异均有统计学意义(均P<0.05),而在性别、年龄、临床分型之间的差异无统计学意义(均P>0.05);单因素分析结果显示喉癌患者HPA蛋白高表达组比HPA低表达组的生存时间更短,HPA高表达组的中位生存时间和5年生存率分别为24个月、43.33%,低表达组分别为56个月、61.54%,未表达组分别为65个月、70.59%。临床分期、T分级、淋巴结是否转移、分化程度与生存时间差异有统计学意义(均P<0.05),而年龄、性别、临床分型与患者的预后差异均无统计学意义(均P>0.05)。多因素COX比例风险回归分析结果提示,淋巴结转移、HPA表达水平和HPA定位是3个独立的喉癌预后因子。此外,HPA表达的细胞定位与喉癌患者的预后密切相关,喉癌组织细胞核HPA染色阳性患者与细胞质HPA染色阳性患者的生存率差异有统计学意义(P<0.05)。结论:HPA阳性表达与较差的生存相关,可以考虑作为一个潜在的预后不良的标志物,HPA在细胞质的定位表达为预后较差的标志,而HPA在细胞核的定位表达则为较好的预后标志。Abstract: Objective:The aim of this study is to explore the expression of heparanase(HPA) in human laryngeal squamous cell carcinoma and its correlation with the clinical pathologic features, such as clinical stage, T grade, lymph node metastasis and cellular differentiation. At the same time, to evaluate the relationship between heparanse localization and expression in human laryngeal squamous cell carcinoma(HLSCC) and tumor prognosis and patients survival.Method:The expression levels of HPA in HLSCC tissues of 73 cases and benign lesions of 38 cases(control) were detected via immunohistochemistry. The correlation of HPA expression with various clinical pathologic features was evaluated with single factor analysis.The Fisher exact test and chi-square tests were used to compare categorical data. Univariate survival was evaluated by Kaplan-Meier curves and tested using log-rank test. Multivariate Cox proportional-hazards regression was used to evaluate independent prognostic factors associated with survival.Result:The positive expression rate of HPA in 73 HLSCC patients and benign lesions of 38 cases were 76.71%(56/73)and 21.05%(8/38) respectively(P<0.05). The clinical pathologic analysis showed that HPA level had a relationship with the clinical stage, T grade, cellular differentiation and lymph node metastasis(P<0.05), while not with gender, age and clinical types(P>0.05). Survival analysis showed that the patients with high HPA expression had significantly poorer outcome as compared with the patients with low HPA expression. The medium survival time and the 5-year survival rate were 24 months and 43.33% in high-heparanase group, 56 months and 61.54% in the low-heparanase group and 65 months and 70.59% in the none-heparanse group(P=0.010). The survival was related to clinical stage, T grade, lymph node metastasis, and cellular differentiation(P<0.05), but not with age, sex and clinical types(P>0.05). In multivariate Cox proportional-hazards regression analysis, the results suggested that lymph node metastasis, hepanranase expression level and heparanase localization were independent prognosis factor for HLSCC. Moreover, hepanranase localization correlated with patient outcome.Kaplan-Meier analysis demonstrated statistically significantly difference for 5-years overall survival rate between the patients with HPA nuclear staining and the patients with HPA cytoplasmic staining(P<0.05).Conclusion:HPA was related with worse overall survival and could be considered as a potential marker of poor prognosis. Cytoplasmic staining of heparanase inversely correlated with patients survival and predicts poor prognosis, whereas nuclear heparanase predicts a favourable outcome.
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Key words:
- laryngeal neoplasms /
- heparanase /
- survival /
- staining /
- localization
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