Wnt-1诱导分泌蛋白-1表达与乳腺癌预后的关系

Relationship between Wnt-1 induced secreted protein-1 expression and prognosis of breast cancer patients

目的探讨Wnt-1诱导分泌蛋白-1(WISP-1)表达与乳腺癌预后的关系。方法本研究选取南昌市第三医院2011年1~6月手术切除且经常规病理证实的浸润性乳腺癌标本120例及其癌旁组织进行回顾性分析。采用免疫组织化学EnVision两步法检测WISP-1蛋白在120例乳腺癌组织及其癌旁组织中的表达,同时收集这些患者的临床特征以及随访结果,采用χ~2检验分析乳腺癌组织中WISP-1表达与患者临床病理特征的关系,采用Kaplan-Meier法计算患者生存率,采用Log-rank检验比较患者生存差异,并用Cox比例风险模型分析影响乳腺癌患者预后的因素。结果 WISP-1在浸润性乳腺癌中的阳性表达率(85%,102/120)明显高于癌旁组织(35%,42/120)(χ~2=7.653,P=0.003)。WISP-1表达与患者的肿瘤组织学分级(χ~2=22.846,P<0.001)、淋巴结转移(χ~2=11.663,P=0.001)、HER-2表达(χ~2=7.825,P=0.005)以及远处转移(χ~2=35.737,P<0.001)有关。患者随访时间为24.0~60.0个月,中位随访时间为43.9个月。生存分析结果发现,WISP-1表达水平是患者DFS的预后因素(χ~2=19.354,P<0.001)。低表达WISP-1的患者出现复发转移的中位时间是48个月,而高表达WISP-1的患者出现复发转移的中位时间是40个月。Cox比例风险模型分析提示,WISP-1(OR=2.129,95%CI:1.099~4.124,P=0.025)、年龄(OR=4.617,95%CI:2.803~7.605,P<0.001)、淋巴结转移(OR=2.014,95%CI:1.209~3.355,P=0.007)是乳腺癌患者DFS的独立预后因素。结论高表达WISP-1的乳腺癌患者预后更差,WISP-1蛋白可能是乳腺癌预后的标志物。

Objective To explore the relationship between the expression of Wnt-1 induced secreted protein-1 （WISP-1） and the prognosis of breast cancer patients. Methods The specimens of breast cancer tissue and adjacent normal breast tissue were collected from 120 cases of invasive breast cancer in Third Hospital of Nanchang City from January to June 2011. The expression of WISP-1 in specimens was measured by immunohistochemical EnVision method. The elinicopathological characteristics and follow-up results were further analyzed. The relationship between WISP-1 expression in breast cancer tissue and elinicopathological characteristics was analyzed using χ^2 test. The survival rate was calculated with Kaplan-Meier method and the survival difference was analyzed with Log-rank test. The Cox proportional hazards model was used to analyze the prognostic factors in breast cancer patients. Results The positive rate of WISP-1 was 85% （102/120） in invasive breast cancer tissue, significantly higher than 35% （42/120） in normal breast tissue （ χ^2 = 7. 653, P = 0. 003 ）. The expression of WISP-1 was correlated with histological grade （χ^2 = 22. 846, P〈0. 001 ） , lymph node metastasis（ χ^2 = 11. 663, P = 0. 001 ）, HER-2 expression （ χ^2 = 7. 825, P = 0. 005 ） and distant metastasis （ χ^2 = 35. 737 ,P〈0. 001 ）. The follow-up time was 24. 0-60.0 months, median 43.9 months. Survival analysis showed that WISP-1 expression was the prognostic factor of DFS （χ^2= 19. 354, P〈0. 001 ）. The median time to recurrence and metastasis was 48 months in patients with low expression of WISP-1, 40 months in patients with high expression of WISP-1. Cox proportional hazards model suggested that WISP-1 expression （ OR = 2. 129, 95% CI： 1. 099-4. 124 ,P= 0. 025 ）, age （ OR=4. 617,95% CI：2. 803-7. 605 ,P〈0. 001 ） and lymph node metastasis （ OR = 2. 014, 95% CI： 1. 209-3. 355, P = 0. 007 ） were independent prognostic factors of DFS in breast cancer patients. Conclusion The breast cancer patients with high expression of WISP-1 have poor prognosis and WISP-1 protein can serve as an index for the prognosis of breast cancer.