鼻咽癌放疗患者血清miR-196a表达的临床意义

Clinical significance of miR-196a expression in serum of patients with nasopharyngeal carcinoma treated with radiotherapy

目的MicroRNAs(miRNAs)属于非编码蛋白基因,是一类负调控基因表达的小RNA,血清中miRNAs具有重要临床意义。为探讨miR-196a在NPC中表达的临床意义,本研究分析血清miR-196a表达水平与NPC放疗反应的相关性。方法收集选取中南大学湘雅医院2010年6月—2019年6月接受调强放疗并有完整随访资料的NPC患者138例作为研究的实验组,同期选取来院健康检查的正常人62例作为对照组。对照组采集空腹静脉血,所有患者均于放疗前采集空腹静脉血,实时荧光定量PCR(qPCR)检测血清miR-196a表达水平;分析血清miR-196a高表达与NPC患者临床分期及无病生存期(DFS)的相关性。以实体瘤变化和随访结果为评判标准,根据疗效将患者分为A组(放疗癌灶完全缓解)和B组(放疗癌灶部分缓解+放疗癌灶稳定进展);进而分析血清miR-196a表达水平与NPC疗效的关系。结果138例NPC患者miR-196a在血清中高表达122例(88.41%);其中86例临床分期Ⅲ、Ⅳ期NPC患者血清miR-196a高表达81例,16例临床分期Ⅰ期NPC患者血清miR-196a高表达14例,36例临床分期Ⅱ期NPC患者血清miR-196a高表达27例;各组NPC血清miR-196a表达与正常对照组比较,差异均具有统计学意义(P均<0.01)。按放疗效果分析,86例A组患者,血清miR-196a高表达71例(82.56%);52例B组患者,血清miR-196a高表达51例(98.08%),包括稳定进展19例(100.00%,19/19)和部分缓解32例(96.97%,32/33);A、B两组血清miR-196a高表达比较,差异具有统计学意义(P<0.01)。A组患者中位DFS(36个月)明显高于B组患者中位DFS(10个月),差异具有统计学意义(P<0.01)。结论血清miR-196a高表达提示临床NPC放疗预后不佳,该基因有望成为NPC预后的血清生物标志物。

Objective MicroRNAs(miRNAs)belong to non-coding protein genes,which are a class of small RNAs that negatively regulate gene expression,and seral miRNAs have important clinical significance.To investigate the clinical significance of miR-196 a level in nasopharyngeal carcinoma(NPC),this study analyzed the relationship between the level of seral miR-196 a and the response to radiotherapy in NPC patients.Methods A total of 138 NPC patients with results of the follow-up after treated with intensity-modulated radiotherapy(IMRT)in Xiangya Hospital from June 2010 to June 2019 were chosen as the experimental group.Fasting venous blood samples of all patients were collected before radiotherapy.In addition,fasting venous blood samples of 62 normal adults who came to the hospital for health examination were collected as controls.And the expression level of serum miR-196 a was detected by real-time fluorescence quantitative polymerase chain reaction(qPCR).The correlation between the high expression of seral miR-196 a and clinical staging related to disease-free survival(DFS)in NPC patients was analyzed.Based on the response evaluation criteria in solid tumors and follow-up results,the patients were divided into Group A(complete response,CR)and Group B(partial response,PR;stable progression,SP).The relationship between the levels of seral miR-196 a and the efficacy of NPC radiotherapy was analyzed.Results MiR-196 a was highly expressed in 122 sera of all the 138 NPC patients(88.41%).In sera of 86 patients in advanced clinical stage(Ⅲ、Ⅳ),miR-196 a was highly expressed in 81 cases.In 16 patients of clinical stageⅠand 36 of clinical stageⅡ,miR-196 a was highly expressed in 14 cases and 27 cases respectively.The level of miR-196 a expression in serum of each NPC group was significantly higher than that in the normal group(all P<0.01).According to the effect of radiotherapy,expression of seral miR-196 a was high in 71 of 86 patients in Group A(82.56%),and 51 of 52(98.08%)in Group B(PR:96.97%,32/33;SP:100%,19/19).The difference of serum miR-196 a high expression between Group A and Group B was statistically significant(P<0.01).The median DFS of Group A(36 months)was significantly higher than that of Group B(10 months)(P<0.01).Conclusions The high expression of seral miR-196 a hints a poor prognosis of NPC after radiotherapy.The miR-196 a gene is expected to be a seral biomarker for the prognosis of NPC.