小细胞肺癌组织中MIP-3α和CCR6表达与术后复发转移及预后的关系

Relationships between Expression of MIP-3 and CCR6 with Postopera-tive Recurrence, Metastasis and Prognosis in Small Cell Lung Cancer

目的 探讨小细胞肺癌 (SCLC) 组织中巨噬细胞炎症蛋白3α (MIP-3α) 和CC趋化因子受体6 (CCR6) 表达与术后复发转移及预后的关系.方法 收集陕西省核工业215医院SCLC癌组织标本 (96例)为SCLC组, 癌旁组织标本 (52例) 为正常组.采用qRT-PCR与免疫组化法检测两组MIP-3α与CCR6 mR-NA相对表达量及蛋白表达情况, Western印迹法检测MIP-3α与CCR6 蛋白表达水平, 采用流式细胞术和ELISA分别测定Th17细胞及其细胞因子白细胞介素-17 ( IL-17)、 IL-21、肿瘤坏死因子-α ( TNF-α) 水平.并分析MIP-3α、 CCR蛋白表达情况与SCLC患者临床病理参数、 Th17细胞及其细胞因子的关系.随访结束后分析SCLC患者术后复发转移与MIP-3α、 CCR6表达的关系.采用logistic回归分析影响SCLC患者术后复发转移的相关因素;Kaplan-Meier法分析SCLC患者预后情况.结果 SCLC组MIP-3α与CCR6 mRNA相对表达量及蛋白表达水平均显著高于正常组 ( P<0.05);MIP-3α、 CCR6表达均与淋巴结转移、临床分期显著相关 (P<0.05);MIP-3α、 CCR6 蛋白表达水平分别与 Th17、 IL-17、 IL-21 水平呈显著正相关 ( P <0.05);术后复发转移SCLC患者MIP-3α、 CCR6 mRNA及蛋白表达水平均显著高于未复发转移者 ( P<0.05);logistic回归分析显示病理分期、 IL-17、 MIP-3α与CCR6水平均为影响术后复发转移的独立危险因素;Kaplan-Meier法分析显示 MIP-3α 与 CCR6 阴性表达组患者 PFS、 OS 均显著高于阳性表达组 ( P <0.05).结论 SCLC患者MIP-3α与CCR6表达水平显著升高, 其高表达水平与术后复发转移及患者预后不良密切相关.

Objective To investigate the relationships between the expression of macrophage inflammatory protein-3α ( MIP-3α ) and CC chemokine receptor 6 ( CCR6 ) in small cell lung cancer ( SCLC) with postoperative recurrence, metastasis and prognosis.Methods SCLC cancer tissue specimens (96 cases) were collected as SCLC group, para cancerous tissue specimens (52 cases) as normal group.The relative expression levels of MIP-3α and CCR6 mRNA and protein were detected by qRT-PCR and immunohistochemistry, the expression levels of MIP-3α and CCR6 protein were detected by Western blotting, the levels of IL-17, IL-21 and TNF-alpha in Th17 cells and their cytokines were measured by flow cytometry and ELISA, respectively.And the relationship between the expression of MIP-3α, CCR protein and the clinicopathological parameters, Th17 cells and cytokines in SCLC patients was analyzed.After follow-up, the relationships between the recur-rence and metastasis of SCLC patients and the expression levels of MIP-3α and CCR6 were ana-lyzed.Logistic method was used to analyze the related factors affecting postoperative recurrence and metastasis of SCLC patients.Kaplan-Meier method was used to analyze the prognosis of SCLC pa- tients.The relative mRNA and protein expression levels of MIP-3α and CCR6 were significantly higher in SCLC group than in normal group ( P <0.05 ) .The expression levels of MIP-3α and CCR6 were significantly positively correlated with lymph node metastasis and clinical stage ( P <0.05).The expression levels of MIP-3 a and CCR6 were positively correlated with Th17, IL-17 and IL-21, respectively ( P<0.05) .The mRNA and protein expression levels of MIP-3α, CCR6 in SCLC patients with recurrence and metastasis were significantly higher than those in SCLC patients without recurrence and metastasis ( P <0.05).Logistic analysis showed that pathological staging, IL-17, MIP-3α and CCR6 levels were independent risk factors for postoperative recurrence and me-tastasis.Kaplan-Meier analysis showed that PFS and OS in the MIP-3α and CCR6 negative group were significantly higher than those in the positive group ( P<0.05).Conclusion The expression levels of MIP-3α and CCR6 in SCLC patients were significantly increased, and their expression lev-els were closely related to postoperative recurrence, metastasis and poor prognosis.