血浆LncRNA-HEIH表达水平与肝癌发病风险的关联分析

摘要

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 AUC. Conclusion:Plasma LncRNA-HEIH expression is posi-tively 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.