甲状旁腺肿瘤诊断中两种lncRNA评分模型的构建

Identification of two lncRNA scores in diagnosis of parathyroid tumors

目的本课题组前期芯片研究发现,ENST00000538790、NR_125790等长链非编码RNA(lncRNA)在甲状旁腺癌及甲状旁腺腺瘤组织标本中的表达存在明显差异,本研究进一步探讨ENST00000538790及NR_125790等lncRNA及其构建的lncRNA评分模型在甲状旁腺癌中的诊断价值。方法收集57例甲状旁腺功能亢进患者的新鲜组织标本,11例为甲状旁腺癌,46例为甲状旁腺腺瘤,采用实时定量PCR(RT-qPCR)技术检测lncRNA ENST00000511928、ENST00000538790、ENST00000618339、NR_125790及ENST00000485384的表达差异,构建lncRNA评分模型,评估模型在甲状旁腺癌诊断中的价值。结果相比甲状旁腺腺瘤,ENST00000511928及ENST00000538790在甲状旁腺癌组中表达显著升高(P<0.05),ENST00000618339、NR_125790及ENST00000485384表达明显下降(P<0.05),其中ENST00000538790及NR_125790为甲状旁腺癌的独立危险因素(P<0.05)。联合ENST00000538790及NR_125790构建的lncRNA模型"log评分"及"logistic评分",在甲状旁腺癌中受试者工作特征曲线下面积分别为0.935及0.943,且曲线下面积大于ENST00000538790与NR_125790及血钙等传统临床诊断指标单独诊断面积(P<0.05)。结论以lncRNA ENST00000538790及NR_125790构建的lncRNA评分模型有可能成为甲状旁腺癌诊断的潜在辅助手段。

Objective Our previous micro-array study revealed that long non-coding RNA(lncRNA),such as ENST00000538790 and NR_125790,were differently expressed in parathyroid carcinoma compared with those in parathyroid adenoma.Diagnostic value of lncRNAs(ENST00000538790 and NR_125790)and scoring models derived from these lncRNAs in parathyroid carcinoma were investigated in this study.Methods Fifty-seven fresh tissue samples from patients with hyperparathyroidism were collected.Eleven patients were diagnosed with parathyroid carcinoma,while 46 patients were found with parathyroid adenoma.The expression levels of five lncRNAs(ENST00000511928,ENST00000538790,ENST00000618339,NR_125790,and ENST00000485384)were detected with realtime quantitative PCR(RT-qPCR).LncRNA scores were calculated using these lncRNAs,and their value in parathyroid carcinoma diagnosis were also assessed.Results It was found that expression levels of ENST00000511928 and ENST00000538790 were up-regulated in parathyroid carcinoma compared with parathyroid adenoma(P<0.05),while the levels of ENST00000618339,NR_125790,and ENST00000485384 were decreased in parathyroid carcinoma(P<0.05).Among these lncRNAs,ENST00000538790 and NR_125790 were independent risk factors for parathyroid carcinoma(P<0.05).Hence,"log score"and"logistic score"were calculated with ENST00000538790 and NR_125790 levels.The areas under the receiver operating characteristic curve for"log score"and"logistic score"were up to 0.935 and 0.943 respectively in parathyroid carcinoma(P<0.05),and were found to be greater than those from single lncRNA or classic clinical indices,such as serum calcium(P<0.05).Conclusion LncRNA scores with lncRNA ENST00000538790 and NR_125790 may play potential role in diagnosis of parathyroid carcinoma.