MicroRNA-125a-5p 表达对弥漫大B 细胞 淋巴瘤耐药及临床预后的影响

Effect of miR-125a-5p expression on drug resistance and clinical prognosis of diffuse large B cell lymphoma

摘要:

目的 检测microRNA-125a-5p（miR-125a-5p）在弥漫性大B 细胞淋巴瘤（DLBCL）组织中的表 达情况，探讨其对肿瘤耐药及预后的影响。方法 收集DLBCL 石蜡标本及其临床病理资料并随访；采用实时 荧光定量聚合酶链反应（qRT-PCR）检测组织中miR-125a-5p 的mRNA 相对表达量；用免疫组织化学染色检 测肿瘤组织中P 糖蛋白（P-gp）、细胞增殖核抗原（Ki-67）蛋白的表达；分析miR-125a-5p 与耐药蛋白Pgp 表达的关系，以及该表达对DLBCL 肿瘤细胞增殖和临床病理特征及预后的影响。结果 MiR-125a-5p 在 DLBCL 组中的表达高于对照组，差异有统计学意义（P <0.05）；其表达量与患者乳酸脱氢酶（LDH）、免疫表 型相关（P <0.05），与年龄、性别、原发部位、临床分期、国际预后指数（IPI）均无相关（P >0.05）；miR- 125a-5p 高表达组P-gp 蛋白阳性率高于低表达组；Kaplan-Meier 及Log-rank 生存分析显示低表达miR- 125a-5p 患者的总生存期（OS）及无复发生存期（RFS）均高于高表达组，COX 风险比例模型分析显示Ann Arbor 分期Ⅲ、Ⅳ期及miR-125a-5p 高表达均可作为DLBCL 患者预后不良的因素。结论 miR-125a-5p 与 DLBCL 耐药蛋白P-gp 表达相关，miR-125a-5p 高表达及Ann Arbor 分期Ⅲ、Ⅳ提示DLBCL 患者预后较差， 可作为潜在的DLBCL 预后预测分子。

Abstract:

Objective To detect the expression of miR-125a-5p in the tissue of diffuse large B cell lymphoma (DLBCL), and to explore its effect on tumor drug resistance and prognosis. Methods DLBCL paraffin specimens and their clinical data were collected, and the patients were followed up to complete the survival data. qRT-PCR was used to detect the relative expression of miR-125a-5p mRNA. Immunohistochemical staining was used for detection of P-gp and Ki67 protein expressions in the tumor tissue. The correlation between miR-125a-5p and resistant protein P-gp expression was statistically analyzed, and the influence of miR-125a-5p expression level on DLBCL cell proliferation and the prognosis was explored. Results miR-125a-5p expression was significantly higher in DLBCL than the reactive hyperplasia group (P < 0.05); its expression quantity was related to LDH level and the immunophenotype of the patients, but not correlated with age, gender, primary site, clinical stage or IPI score (P > 0.05). The positive expression rate of P-gp protein in the miR-125a-5p high-expression group was higher than that in the miR-125a-5p low-expression group. Kaplan-Meier and Log-rank survival analyses showed that the overall survival and recurrence-free survival of the patients with low expression of miR-125a-5p were higher than those of the high-expression group. COX risk proportion model analysis showed that Arbor stages III and IV and miR-125a-5p high expression are the independent factors of poor prognosis of the patients with DLBCL. Conclusions The expression of miR-125a-5p is associated with the expression level of drug resistant protein P-gp in DLBCL. High expression of miR-125a-5p and Arbor stages III and IV indicate poor prognosis of the patients with DLBCL. And miR-125a-5p can be used as a potential molecule for prediction of the prognosis of DLBCL.