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Ln-cRNA-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。
Objective:To quantitatively examine expression of LncRNA-HEIH in plasma of patients with hepato-cellular carcinoma( HCC)and to evaluate its utility as a risk predictor for HCC. Methods:Blood samples were col-lected 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 ex-amine the change in LncRNA-HEIH expression. Twelve cancerous tissues were also obtained from these patients af-ter 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 charac-teristic( 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 cor-relation 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 be-tween 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 A