弥漫大B细胞淋巴瘤组织TLR4和CD163及CD206表达临床意义

Expressions of Toll like receptor 4 and CD163 CD206 in diffuse large B-cell lymphoma and their clinical significance

目的弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后因素尚不明确.本研究探讨TLR4、CD163和CD206在DLBCL组织表达及临床意义,并寻找新的DLBCL预后指标.方法回顾性分析2011-06-01-2017-06-30中南大学湘雅医学院附属海口医院确诊的84例DLBCL患者,收集患者临床资料、治疗及预后信息,采用免疫组织化学法检测DLBCL组织中TLR4、CD163和CD206分子表达,分析其表达程度与临床病理特征及预后关系,组间比较采用χ^2检验,应用Kaplan-Meier法绘制生存曲线,Log-rank法进行曲线间单因素分析,多因素分析采用Cox回归模型.结果 TLR4蛋白表达阳性与LDH水平升高有关联,其中LDH水平升高者占TLR4蛋白表达阳性患者的58.1%(25/43),差异有统计学意义,χ^2=4.858,P=0.031.TLR4、CD163和CD206蛋白表达在患者年龄、性别、Ann Arbor分期、美国东部肿瘤协作组评分、国际预后指数评分、B症状、Hans法分型之间差异均无统计学意义,均P>0.05.Spearman秩次相关分析结果显示,在DLBCL组织中TLR4与CD163(r=0.167,P=0.190)和CD206表达(r=0.191,P=0.087)无关联.单因素分析显示,年龄(χ^2=5.192,P=0.023)、TLR4(χ^2=5.772,P=0.016)和CD206表达水平(χ^2=4.575,P=0.032)与中位无进展生存期有关联,CD206表达水平(χ^2=5.060,P=0.024)与中位总生存期有关联.多因素分析显示,TLR4(HR=1.755,P=0.019)和CD206(HR=1.638,P=0.036)是影响无进展生存期独立预后危险性因素;CD206(HR=1.668,P=0.029)是影响总生存期独立预后危险性因素.结论TLR4和CD206蛋白表达对判断DLBCL患者预后有一定临床价值,有望成为评估DLBCL预后的新指标.

OBJECTIVE The prognostic factors of diffuse large B-cell lymphoma(DLBCL) are still unclear. This study aimed to investigate the expressions of Toll like receptor 4(TLR4),CD163 and CD206 in DLBCL and their relationship with clinical pathological characteristics of the patients for new prognostic indicators. METHODS The protein expressions of TLR4 ,CD163 and CD206 were immunohistochemically detected in samples of 84 DLBCL tissues diagnosed in Affiliated Haikou Hospital of Xiangya Medical College from June 1st,2011 to June 30th,2017. The clinicopathological data,treatment and prognosis information of patients were collected. The expressions of TLR4,CD163 and CD206 molecules in DLBCL tissues were detected by immunohistochemistry, and the relationships between the expression level and the clinicopathological characteristics and prognosis were analyzed. Kaplan-Meier method was used to draw the survival curve,and Log-rank method was used for single factor analysis among the curves Cox regression model was used for multivariate analysis. RESULTS Positive TLR4 protein expression was associated with an increase in LDH level, and the increase of LDH level accounted for 58. 1%(25/43 cases) of TLR4 protein expression positive patients,with statistically significant difference (χ^2=4. 858,P = 0. 031). The expression of TLR4 ,CD163,and CD206 showed no significant difference between the age,gender, Ann Arbor staging,ECOG score,IPI score,B-symptom and Hans classification. Spearman rank correlation analysis showed that there was no correlation between TLR4 and CD163 ,CD206 expression in DLBCL tissues (r=0. 167, P = 0. 190;r=0. 191,P = 0. 087). Univariate analysis showed that age and the expression level of TLR4,CD206 had impacts on PFS (χ^2=5. 192,P=0.023;χ^2=5. 772,P=0. 016;χ^2=4. 575,P = 0. 032). The expression levels of CD206 had an impact on OS (χ^2 =5. 060,P = 0. 024). Multivariate analysis showed that TLR4 and CD206 were independent prognostic factors influencing PFS(HR=1. 755,P = 0. 019;HR= 1. 638,P=0. 036) and CD206 was independent prognostic factor influencing OS ( HR = 1. 668, P = 0. 029). CONCLUSION The expression of TLR4 and CD206 protein has certain clinical value in judging the prognosis of DLBCL patients, which is expected to become a new indicator for the prognosis of DLBCL.