Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Endocr Relat Cancer. 2019 Feb;26(2):163-176. doi: 10.1530/ERC-18-0480.
Parathyroid carcinoma (PCa) is a rare endocrine neoplasia that typically has unfavourable outcomes. The contribution of long non-coding RNAs (lncRNAs) to the development of malignant and benign parathyroid tumours remains largely unknown. In this study, we explored transcriptomic profiling of lncRNA and mRNA expression in 6 PCa, 6 parathyroid adenoma (PAd) and 4 normal parathyroid (PaN) tissues. In total, 2641 lncRNA transcripts and 2165 mRNA transcripts were differentially expressed between PCa and PAd. Enrichment analysis demonstrated that dysregulated transcripts were involved mainly in the extracellular matrix (ECM)-receptor interaction and energy metabolism pathways. Bioinformatics analysis suggested that ATF3, ID1, FOXM1, EZH2 and MITF may be crucial to parathyroid carcinogenesis. Series test of cluster analysis segregated differentially expressed lncRNAs and mRNAs into several expression profile models, among which the 'plateau' profile representing components specific to parathyroid carcinogenesis was selected to build a co-expression network. Seven lncRNAs and three mRNAs were selected for quantitative RT-PCR validation in 16 PCa, 41 PAd and 4 PaN samples. Receiver-operator characteristic curves analysis showed that lncRNA PVT1 and GLIS2-AS1 yielded the area under the curve values of 0.871 and 0.860, respectively. Higher hybridization signals were observed in PCa for PVT1 and PAd for GLIS2-AS1. In conclusion, the current evidence indicates that PAd and PCa partially share common signalling molecules and pathways, but have independent transcriptional events. Differentially expressed lncRNAs and mRNAs have intricate interactions and are involved in parathyroid tumourigenesis. The lncRNA PVT1 and GLIS2-AS1 may be new potential markers for the diagnosis of PCa.
甲状旁腺癌（PCa）是一种罕见的内分泌肿瘤，通常预后不良。长链非编码 RNA（lncRNA）在恶性和良性甲状旁腺瘤发生发展中的作用尚不清楚。本研究通过对 6 例 PCa、6 例甲状旁腺腺瘤（PAd）和 4 例正常甲状旁腺（PaN）组织的 lncRNA 和 mRNA 表达进行转录组谱分析。结果显示，PCa 和 PAd 之间共有 2641 个 lncRNA 转录本和 2165 个 mRNA 转录本差异表达。富集分析表明，失调的转录本主要参与细胞外基质（ECM）-受体相互作用和能量代谢途径。生物信息学分析提示 ATF3、ID1、FOXM1、EZH2 和 MITF 可能是甲状旁腺癌发生的关键因素。系列聚类分析测试将差异表达的 lncRNA 和 mRNA 分为几种表达谱模型，其中“高原”模式代表了甲状旁腺癌发生的特定成分，被用于构建共表达网络。在 16 例 PCa、41 例 PAd 和 4 例 PaN 样本中，对 7 个 lncRNA 和 3 个 mRNA 进行了定量 RT-PCR 验证。ROC 曲线分析显示，lncRNA PVT1 和 GLIS2-AS1 的曲线下面积分别为 0.871 和 0.860。在 PCa 中，PVT1 的杂交信号较高，在 PAd 中，GLIS2-AS1 的杂交信号较高。总之，目前的证据表明，PAd 和 PCa 部分共享共同的信号分子和途径，但有独立的转录事件。差异表达的 lncRNA 和 mRNA 之间存在复杂的相互作用，参与了甲状旁腺瘤的发生。lncRNA PVT1 和 GLIS2-AS1 可能是 PCa 诊断的新的潜在标志物。
