Qiu Zhong-Ling, Shen Chen-Tian, Sun Zhen-Kui, Wei Wei-Jun, Zhang Xin-Yun, Song Hong-Jun, Luo Quan-Yong
Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Cell Physiol Biochem. 2016;40(6):1377-1390. doi: 10.1159/000453190. Epub 2016 Dec 19.
The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases.
The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis.
Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(P<0.001).
ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC.
本研究旨在探索血浆长链非编码RNA(lncRNAs)作为诊断甲状腺乳头状癌(PTC)非131I摄取性肺转移的新型生物标志物,并研究PTC肺转移患者血浆lncRNA表达水平与生存的相关性。
使用lncRNA微阵列芯片检测lncRNAs的表达。通过定量逆转录聚合酶链反应验证在非131I摄取性肺转移的PTC患者和131I摄取性肺转移的PTC患者之间表达差异最显著的lncRNAs。采用Kaplan-Meier方法确定血浆lncRNA水平是否可指示患者预后。
与131I摄取性肺转移相比,我们发现在PTC的非131I摄取性肺转移中,两个lncRNAs(ENST00000462717和ENST00000415582)上调,两个(TCONS_00024700和NR_028494)下调。受试者工作特征曲线(ROC)分析表明,使用这四种lncRNAs对预测PTC的非131I摄取性肺转移具有较高的诊断敏感性和特异性。在训练集和验证集中,ENST00000462717、ENST00000415582、TCONS_00024700和NR_028494的曲线下合并面积分别为0.890、0.936、0.975和0.918。还发现低血浆lncRNA水平(ENST00000462717和ENST00000415582)和高血浆lncRNA水平(TCONS_00024700和NR_028494)与PTC肺转移患者的较好预后相关(P<0.001)。
ENST00000462717、ENST00000415582、TCONS_00024700和NR_028494可作为PTC非131I摄取性肺转移诊断和预后评估的新型微创标志物。