血浆LncRNA-HEIH表达水平与肝癌发病风险的关联分析

目的:探讨血浆长片段非编码RNA HEIH（LncRNA-HEIH）表达水平与肝细胞肝癌（HCC）发病风险的关系并初步探讨其临床应用价值。方法:收集179例首治的HCC和179例年龄、性别与HCC患者相匹配的健康志愿者的外周血样本，运用荧光定量PCR 方法检测各组血浆LncRNA-HEIH表达水平，比较分析血浆LncRNA-HEIH表达水平与HCC发病风险的关系；同时，收集病例组患者术后7天血浆标本40例及肝癌组织12例，分析术前、术后血浆LncRNA-HEIH的表达变化及肝癌组织和对应的外周血浆中LncRNA-HEIH表达水平的相关性；另外，分析术前血浆LncRNA-HEIH表达与患者临床病理特征间的关系，并绘制研究对象工作特征曲线（ROC）。结果:HCC患者血浆LncRNA-HEIH表达水平显著高于健康对照组（中位数:2.18 vs 1.70，P<0.001），随着TNM分期的增加，血浆LncRNA-HEIH的表达水平逐渐升高（Ⅰ期、Ⅱ期、Ⅲ期及Ⅳ期中位数分别为1.83、2.36、2.82和3.45，各组间比较P值均小于0.05）。术前HCC患者血浆和癌组织中LncRNA-HEIH的表达存在显著相关性（r=0.636，P=0.026）。术后患者血浆 LncRNA-HEIH的表达较术前明显降低（中位数:2.15 vs 1.59，P<0.001）。以健康对照为参照，与LncRNA-HEIH表达低的个体相比，血浆LncRNA-HEIH表达高的个体HCC发病风险显著上升（adjusted OR=1.96；95%CI:1.28-2.99），且高的血浆LncRNA-HEIH表达水平与HCC发病风险之间存在显著的剂量依赖关系（P<0.001）。用血浆LncRNA-HEIH表达水平绘制ROC曲线，曲线下面积为0.681（95%CI:0.626-0.736），明显优于AFP（AUC=0.638，95%CI:0.581-0.695），联合LncRNA-HEIH和AFP可显著提高单独运用AFP或LncRNA-HEIH诊断肝癌的效力（AUC=0.714，95%CI:0.671-0.757，P=0.001）。结论:血浆LncRNA-HEIH表达水平与肝癌发病风险显著正相关，可作为HCC发病监测及HCC早期诊断的检测指标。

Association between expression of LncRNA-HEIH in plasma and hepatocellular carcino-ma risk:A case-control study

Objective:To quantitatively examine expression of LncRNA-HEIH in plasma of patients with hepatocellular carcinoma(HCC) and to evaluate its utility as a risk predictor for HCC.Methods:Blood samples were collected from 179 HCC and 179 matched healthy controls for quantitative analysis of plasma LncRNA-HEIH using real-time RT-PCR based method.Forty plasma samples were collected from these patients 7 days after operation to examine the change in LncRNA-HEIH expression.Twelve cancerous tissues were also obtained from these patients after operation to evaluate the correlation of LncRNA-HEIH expression between cancerous tissue and paired plasma.The clinical association of plasma LncRNA-HEIH expression with HCC was analyzed and receiver operating characteristic(ROC) curve was performed to predict the risk of HCC by LncRNA-HEIH expression in plasma.Results:HCC patients exhibited statistically significantly higher plasma LncRNA-HEIH expression than matched controls(median:2.18 vs 1.70；P<0.001).Increased plasma LncRNA-HEIH expression was positively related to TNM stage in HCC patients(all P<0.05).Spearman correlation analysis showed that there was a significant positive correlation for LncRNA-HEIH expression between cancerous tissue and paired preoperative plasma(r=0.636，P=0.026).Compared with individuals who had lower plasma LncRNA-HEIH expression，individuals who had higher plasma LncRNA-HEIH expression had a significantly increased risk of HCC(adjusted OR=1.96；95%CI:1.28-2.99) when healthy controls were used as the reference group.A significant dose-response relation was observed between HCC risk and higher plasma LncRNA-HEIH expression (P for trend <0.001).In addition，the area under the ROC curve performed by the plasma LncRNA-HEIH from all participants was 0.681(95%CI:0.626-0.736).The combined model of AFP and LncRNA-HEIH showed a significantly better prediction efficacy of HCC than either AFP of LncRNA-HEIH only model with the largest AUC.Conclusion:Plasma LncRNA-HEIH expression is positively related with the risk of HCC.It could be used in monitoring the occurrence of HCC and may be a potential marker for early diagnosis of HCC.