肝细胞癌患者肝动脉化疗栓塞术后外周血长链非编码RNA TINCR水平与Th1/Th2平衡及预后的相关性分析

Association of the expression level of the long non-coding RNA TINCR in peripheral blood with Th1/Th2 balance and prognosis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma

目的探讨分析外周血长链非编码RNA(lncRNA)TINCR表达水平与肝细胞癌(HCC)患者行肝动脉化疗栓塞术(TACE)术后辅助性T淋巴细胞1(Th1)/Th2平衡及预后的相关性。方法回顾性选取2015年3月—2017年3月在湖北省武汉市金银潭医院行TACE治疗的HCC患者85例,并随机抽取在本院体检的健康志愿者30例作为对照组。检测HCC患者TACE完成后7 d及对照组外周血lncRNA TINCR表达情况、Th1/Th2细胞因子表达情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验,等级资料组间比较采用Kruskal-Wallis H检验。lncRNA TINCR相对表达量与Th1/Th2细胞因子的相关性采用Spearman相关性分析。lncRNA TINCR相对表达量对生存情况的影响采用Kaplan-Meier生存曲线分析,生存曲线比较采用log-rank检验。结果HCC组患者外周血lncRN TINCR相对表达量(1.784±0.429)高于对照组(0.926±0.263),差异有统计学意义(t=10.277,P<0.05)。lncRNA TINCR相对表达与HCC患者血管侵犯、肿瘤大小、肿瘤分期及血清AFP水平有关(t值分别为3.958、4.499、3.361、4.949,P值分别为<0.001、<0.001、0.001、<0.001)。HCC组患者血清IFNγ、IL-2水平明显低于对照组[(13.48±5.20)pg/ml vs(27.49±7.21)pg/ml、(21.89±6.45)pg/ml vs(32.05±7.89)pg/ml,t值分别为11.408、6.986,P值均<0.05],而IL-4、IL-10水平明显高于对照组[(13.73±3.35)pg/ml vs(9.36±2.73)pg/ml、(12.75±2.74)pg/ml vs(8.93±2.16)pg/ml,t值分别为6.426、6.909,P值均<0.05]。HCC患者外周血lncRNA TINCR相对表达量与血清IFNγ、IL-2水平呈负相关(r值分别为-3.164、-3.270,P值均<0.001),与患者血清IL-4、IL-10呈正相关(r值分别为2.963、3.044,P值分别为0.007、<0.001)。以lncRNA TINCR相对表达量≥1.700作为高表达,85例HCC患者中lncRNA TINCR高表达患者47例,低表达患者38例。log-rank检验结果显示,lncRNA TINCR低表达患者生存情况明显优于高表达患者(χ2=4.182,P<0.05)。结论HCC患者行TACE后外周血lncRNA TINCR表达明显高于健康人群,lncRNA TINCR表达与患者病理特征及Th1/Th2免疫平衡有密切联系,可作为患者生存预后的潜在预测指标之一。

Objective To investigate the association of the expression level of the long non-coding RNA(lncRNA)TINCR in peripheral blood with Th1/Th2 balance and prognosis after transcatheter arterial chemoembolization(TACE)in patients with hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the clinical data of 85 patients with HCC who were treated with TACE in Jinyintan Hospital from March 2015 to March 2017,and 30 healthy volunteers who underwent physical examination in our hospital were randomly selected as control group.The expression of lncRNA TINCR and Th1/Th2 cytokines in peripheral blood were measured on day 7 after TACE for HCC patients and the control group.The t-test was used for comparison of continuous data,the chi-square test was used for comparison of categorical data,and the Kruskal-Wallis H test was used for comparison of ranked data.A Spearman correlation analysis was used to investigate the correlation of the relative expression of lncRNA TINCR with Th1/Th2 cytokines.The Kaplan-Meier survival curves were used to investigate the influence of the relative expression of lncRNA TINCR on survival,and the log-rank test was used for comparison of survival curves.Results The HCC group had significantly higher relative expression of lncRNA TINCR in peripheral blood than the control group(1.784±0.429 vs 0.926±0.263,t=10.277,P<0.05).The relative expression of lncRNA TINCR was associated with vascular invasion,tumor size,tumor stage,and serum alpha-fetoprotein(t=3.958,4.499,3.361,and 4.949,P<0.001,P<0.001,P=0.001,and P<0.001).Compared with the control group,the HCC group had significantly lower serum levels of interferon-γ(IFNγ)[(13.48±5.20)pg/ml vs(27.49±7.21)pg/ml,t=11.408,P<0.05]and interleukin-2(IL-2)[(21.89±6.45)pg/ml vs(32.05±7.89)pg/ml,t=6.986,P<0.05]and significantly higher serum levels of interleukin-4(IL-4)[(13.73±3.35)pg/ml vs(9.36±2.73)pg/ml,t=6.426,P<0.05]and interleukin-10(IL-10)[(12.75±2.74)pg/ml vs(8.93±2.16)pg/ml,t=6.909,P<0.05].In HCC patients,the relative expression of lncRNA TINCR in peripheral blood was negatively correlated with the serum levels of IFNγand IL-2(r=-3.164 and-3.270,both P<0.001)and was positively correlated with the serum levels of IL-4 and IL-10(r=2.963 and 3.044,P=0.007 and P<0.001).With the relative expression of lncRNA TINCR of≥1.700 as high expression,there were 47 HCC patients with high expression and 38 HCC patients with low expression.The log-rank test showed that the patients with low expression of lncRNA TINCR had significantly better survival than those with high expression(χ^2=4.182,P<0.05).Conclusion HCC patients have significantly higher expression of lncRNA TINCR in peripheral blood than the healthy population,and the expression of lncRNA TINCR is closely associated with the pathological features and Th1/Th2 immune balance of patients and can thus be used as one of the potential indicators for predicting the survival and prognosis of patients.