髓样分化因子88及Toll样受体4对新疆地区乳腺癌预后的影响

目的 目前乳腺癌仍然是全球女性死亡的主要原因之一，肿瘤的远处转移是乳腺癌患者规范化治疗后的首要致死原因。本研究通过分析乳腺癌患者的预后与固有免疫应答物髓样分化因子88(myeloid differentiation primary response 88,MyD88)和Toll样受体4(toll-like receptor 4，TLR4)的关系以确定对乳腺癌预后的影响。 方法 本研究分析了2005—2007年新疆医科大学第一附属医院乳腺外科200例乳腺浸润性导管癌患者的临床、病理资料，并且对总生存期(overall survival，OS)以及无病生存期(disease free survival，DFS)进行了分析。 结果 153名(76.50%)患者是无复发转移的，47名(23.50%)为复发或者转移的患者。MyD88和TLR4之间是有着显著的相关性(P<0.001)。高表达MyD88和TLR4的患者更容易发生死亡及复发/转移事件(P<0.05)。低表达MyD88及TLR4较二者均高表达的患者表现出更长时间的DFS及OS (log-rank test，P<0.05)。低表达MyD88及TLR4的较二者任一高表达的患者表现出更长时间的DFS及OS (log-rank test，P<0.001)。在多因素分析中，MyD88的高表达是DFS的独立不良预后因素(adjusted HR为3.322;95%CI:1.663～6.631;P=0.001)，同样预示着较低的OS (adjusted HR为4.500;95%CI:1.544～13.098;P=0.005)。 结论 TLR4-MyD88信号通路的活化或者MyD88的活化将会预示着乳腺癌患者不良的预后，二者将会成为乳腺癌新的生物调节治疗的新靶点。 

Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients in Xinjiang

Objective Breast cancer remains a major cause of death in women worldwide,and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment.This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response:myeloid differentiation primary response 88(MyD88) and Toll-like receptor 4(TLR4). Methods We analyzed data of 200 breast invasive ductal carcinoma(IDC) patients who were treated at the department of breast surgery,the First Affiliated Hospital of Xinjiang Medical University from 2005 to 2007.Overall survival(OS) and disease free survival(DFS) were compared. Results In total,153 patients(76.50%) were disease-free without relapse or metastasis,whereas 47(23.50%) patients developed recurrence or metastasis.A significant positive correlation was observed between MyD88 and TLR4 expression(P<0.001).Patients with high expression were more likely to experience death and recurrence/metastasis events(P<0.05).Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels(log-rank test,P<0.001).Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test,P<0.001).In a multivariate analysis,high MyD88 expression was an independent predictive factor for decreased DFS(adjusted HR,3.322;95% CI:1.663-6.631;P=0.001) and OS (adjusted HR,4.500;95% CI:1.544-13.098;P=0.005). Conclusion TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer.Therefore,TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.