共刺激分子CD80和CD86表达对鼻咽癌进展及预后的影响研究

摘要

背景 CD80和CD86是T淋巴细胞活化的重要共刺激分子，肿瘤细胞可通过低表达或缺失共刺激分子发生免疫逃逸。目的探讨共刺激分子CD80和CD86表达对鼻咽癌进展和预后的影响。方法选取2001年1月—2003年12月经中山大学肿瘤防治中心病理科诊断为鼻咽癌并有相应临床随访资料的鼻咽癌组织标本557例。患者均初次诊断且未进行任何治疗，随访时间2~114个月，随访过程中发生转移113例，死亡235例。采用免疫组织化学法检测CD80和CD86表达，采用Kaplan-Meier生存曲线、Log-rank检验及单因素Cox比例风险回归分析探讨CD80和CD86表达与鼻咽癌患者进展及预后的关系。结果免疫组织化学法发现，CD80和CD86主要定位在细胞膜上，在肿瘤间质很少表达。557例患者中CD80低表达组309例，CD80高表达组248例；CD86低表达组470例，CD86高表达组87例。Kaplan-Meier生存曲线和Log-rank检验结果显示，CD80低表达组与CD80高表达组鼻咽癌患者无瘤生存时间比较，差异无统计学意义（χ2＝3.551，P＝0.060）；CD80低表达组与 CD80高表达组鼻咽癌患者总生存时间比较，差异有统计学意义（χ2＝5.521，P＝0.019）。CD86低表达组与CD86高表达组鼻咽癌患者无瘤生存时间及总生存时间比较，差异无统计学意义（χ2＝0.948，P＝0.330；χ2＝0.662，P＝0.416）。单因素Cox比例风险回归分析结果显示，CD80高表达组鼻咽癌患者发生转移复发及死亡的风险高于CD80低表达组（P﹤0.05）；CD86低表达组与CD86高表达组鼻咽癌患者发生转移复发及死亡的风险比较，差异无统计学意义（ P﹥0.05）。Spearman秩相关分析结果显示，鼻咽癌组织中CD86表达与间质中CD68＋巨噬细胞数量呈正相关（rs ＝0.103，P＝0.015）。结论鼻咽癌组织中CD80高表达与鼻咽癌患者预后差有关，增加局部复发和远处转移风险；未发现CD86表达与鼻咽癌患者进展及预后相关。%Background CD80 and CD86 costimulatory molecules have an important role in T cell activation. Low or loss expression of CD80 and CD86 may lead to the occurrence of tumor immune escape. Objective To investigate the influence of CD80 and CD86 expression on the progression and prognosis of nasopharyngeal carcinoma(NPC). Methods 557 cases,who were diagnosed with nasopharyngeal carcinoma from January 2001 to December 2003 in Sun Yat-Sen University Cancer Center were selected in this study. The cases were pathologically confirmed diagnosis of nasopharyngeal carcinoma with biopsy specimens of corresponding clinical follow-up data. Patients were first diagnosed with NPC without any treatment. During the 2 to 114 months follow-up period,113 patients had distant organ metastasis,235 cases occurred to death. Immunohistochemical method was applied to detect CD80 and CD86 expression;Kaplan-Meier survival curve,the Log-rank test and single factor Cox proportional hazards regression analysis were adopted to analyze the relationship between the CD80 and CD86 expression and the progression and the prognosis of NPC patients. Results Immunohistochemical method found that CD80 and CD86 were mainly expressed in tumor cell membrane surface,but little expressed in tumor stroma. Among the 557 patients,309 cases in the low expression group of CD80 ,248 in the high expression group of CD80;470 cases in the low expression group of CD86 ,87 in the high expression group of CD86 . Kaplan-Meier survival curve and the Log-rank test results showed that there was no significant difference in the disease-free survival time between NPC patients in low expression group and high expression group of CD80 (χ2 =3. 551,P=0. 060);and there was significant difference in the overall survival time between NPC patients in low expression group and high expression group of CD80 (χ2 =5. 521,P=0. 019). There were no significant difference in disease-free survival time and the overall survival time between NPC patients in low expression group and high expression group of CD86 (χ2 =0. 948,P =0. 330;χ2=0. 662,P=0. 416). The results of single factor Cox proportional hazards regression analysis showed that the risk of metastasis and recurrence and death of NPC patients in high expression group of CD80 were higher those that of patients in low expression group of CD80(P﹤0. 05);there were no significant difference in the risk of metastasis and recurrence and death of NPC patients in low expression group and high expression group of CD86(P﹥0. 05). Spearman correlation analysis showed that CD86 of NPC tissues was positively correlated with CD68 + macrophages numbers in NPC stroma(rs =0. 103,P=0. 015). Conclusion High expression of CD80 in NPC tissues is negatively correlated with the prognosis of NPC patients,which increases the risk of local recurrence and distant metastasis. The relationship between expression of CD86 and the progression and prognosis of NPC patients is not found.