血清miRNA‑126、miRNA‑449a表达在非小细胞肺癌培美曲塞联合顺铂治疗效果和预后评估中的意义

Significance of serum miRNA⁃126 and miRNA⁃449a expression levels in the therapeutic efficacy and prognostic evaluation of pemetrexed combined with cisplatin for treatment of non⁃small cell lung cancer

目的探讨血清miRNA‑126(miR‑126)、miRNA‑449a(miR‑449a)的表达水平对培美曲塞联合顺铂治疗非小细胞肺癌(NSCLC)的效果和预后的评估作用。方法回顾性分析2016年1月至2017年1月武汉市汉口医院收治的100例采用培美曲塞联合顺铂治疗的NSCLC患者资料,治疗前通过实时荧光定量聚合酶链反应检测血清中miR‑126、miR‑449a相对表达水平。以100名同期体检的健康志愿者为健康对照组。治疗2个疗程后进行疗效评估。分析miR‑126、miR‑449a相对表达水平与患者临床病理特征、疗效及预后的关系。结果NSCLC患者组血清miR‑126、miR‑449a相对表达水平均低于健康对照组(1.23±0.34比2.22±0.57,0.95±0.21比2.13±0.43),差异均有统计学意义(t值分别为14.92、24.66,均P<0.01)。不同疗效NSCLC患者血清miR‑126、miR‑449a相对表达水平差异均有统计学意义(F值分别为80.65、22.43,均P<0.01)。Spearman相关分析显示,血清miR‑126、miR‑449a相对表达水平与疗效具有相关性(ρ值分别为0.782、0.618,均P<0.01)。不同性别和年龄NSCLC患者血清miR‑126、miR‑449a相对表达水平差异均无统计学意义(均P>0.05),不同TNM分期、病理类型、肿瘤长径、分化程度NSCLC患者血清miR‑126、miR‑449a相对表达水平差异均有统计学意义(均P<0.05)。单因素Cox回归分析结果显示TNM分期、肿瘤直径、分化程度、miR‑126相对表达水平、miR‑449a相对表达水平与NSCLC患者生存相关(均P<0.05)。多因素Cox回归分析发现,TNM分期、肿瘤长径、分化程度、miR‑126相对表达水平、miR‑449a相对表达水平是影响NSCLC患者术后生存的独立因素。miR‑126、miR‑449a高表达患者的总生存均优于低表达患者(均P<0.05)。结论血清中miR‑126、miR‑449a相对表达水平可能是培美曲塞联合顺铂治疗的NSCLC患者预后预测的潜在血清学指标。

Objective To investigate the effects of serum miRNA‑126(miR‑126)and miRNA‑449a(miR‑449a)expression levels on the efficacy and prognostic evaluation of pemetrexed combined with cisplatin in treatment of non‑small cell lung cancer(NSCLC).Methods The data of 100 NSCLC patients admitted to Wuhan Hankou Hospital from January 2016 to January 2017 were retrospectively analyzed.Before treatment,the relative expression levels of miR‑126 and miR‑449a in serum of both groups were detected by using realtime fluorescence quantitative polymerase chain reaction.A total of 100 healthy volunteers during the same period were treated as the control group.The efficacy was evaluated after 2 courses of treatment,and the correlation of miR‑126 and miR‑449a relative expression levels with clinicopathological characteristics,efficacy and prognosis of patients was analyzed.Results The relative expression levels of serum miR‑126 and miR‑449a in NSCLC patients were lower than those in the control group(1.23±0.34 vs.2.22±0.57,0.95±0.21 vs.2.13±0.43),and the differences were statistically significant(F=14.92,24.66;all P<0.01).There were significant differences in the relative expression levels of serum miR‑126 and miR‑449a in NSCLC patients with different therapeutic effects(F=80.65,22.43,all P<0.01).Spearman correlation analysis showed that the relative expression levels of serum miR‑126 and miR‑449a were correlated with the therapeutic effect(ρ=0.782,0.618,all P<0.01).The relative expression levels of serum miR‑126 and miR‑449a in NSCLC patients with different gender and age had no statistically significant difference(all P>0.05).The relative expression levels of serum miR‑126 and miR‑449a in NSCLC patients with different TNM staging,pathological type,tumor diameter,degree of differentiation showed significant differences(all P<0.05).Univariate Cox regression analysis showed TNM staging,tumor diameter,degree of differentiation,relative expression levels of serum miR‑126 and miR‑449a were correlated with the survival of NSCLC patients(all P<0.05).Multivariate Cox regression analysis revealed TNM staging,tumor diameter,degree of differentiation and the relative expression levels of miR‑126 and miR‑449a were independent factors affecting the survival of NSCLC patients after surgery.The overall survival of patients with the high expressions of miR‑126 and miR‑449a was better than that of patients with the low expressions(all P<0.05).Conclusions The relative expression levels of serum miR‑126 and miR‑449a can be used as a potential serologic indicator to analyze the prognosis of NSCLC patients treated with pemetrexed combined with cisplatin.