Wu S-C, Chi S-Y, Rau C-S, Kuo P-J, Huang L-H, Wu Y-C, Wu C-J, Lin H-P, Hsieh C-H
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan.
Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan.
J Endocrinol Invest. 2021 Nov;44(11):2375-2386. doi: 10.1007/s40618-021-01543-2. Epub 2021 Mar 1.
This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors.
The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction.
Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers.
We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.
本研究旨在鉴定蛋白质、信使核糖核酸（mRNA）和长链非编码核糖核酸（lncRNA）的潜在循环生物标志物，以区分甲状腺乳头状癌与甲状腺良性肿瘤。
100名患者的研究人群分为鉴定组（10例甲状腺乳头状癌患者和10例甲状腺良性肿瘤患者）和验证组（45例甲状腺乳头状癌患者和35例甲状腺良性肿瘤患者）。使用Sengenics免疫组蛋白阵列结合使用开放靶点平台的数据挖掘方法来鉴定假定的蛋白质生物标志物，并使用酶联免疫吸附测定法验证其表达。通过Illumina HiSeq进行的下一代测序用于检测失调的mRNA和lncRNA。网站Timer v2.0有助于鉴定假定的mRNA生物标志物，这些标志物在甲状腺乳头状癌中比在相邻正常甲状腺组织中显著过度表达。通过实时聚合酶链反应验证mRNA和lncRNA生物标志物的表达。
虽然已鉴定出假定的蛋白质和mRNA生物标志物，但在验证队列中无法确认其血清表达。此外，鉴定并验证了7种lncRNA（TCONS_00516490、TCONS_00336559、TCONS_00311568、TCONS_00321917、TCONS_00336522、TCONS_00282483和TCONS_00494326）在甲状腺乳头状癌患者中与甲状腺良性肿瘤患者相比显著下调。基于预测甲状腺乳头状癌发生的受试者工作特征曲线下面积（AUC = 0.736），这7种lncRNA显示出中等准确性。
我们鉴定出7种下调的循环lncRNA，具有预测甲状腺乳头状癌发生的潜力。
