Department of Endocrine Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China (mainland).
Med Sci Monit. 2019 Dec 19;25:9752-9769. doi: 10.12659/MSM.917845.
BACKGROUND Thyroid carcinoma is a malignancy with high morbidity and mortality. Genetic alterations play pivot roles in the pathogenesis of thyroid carcinoma, where long noncoding RNA (lncRNA) have been identified to be crucial. This study sought to investigate the biological functions of lncRNA expression profiles in thyroid carcinoma. MATERIAL AND METHODS The lncRNAs expression profiles were acquired from The Cancer Genome Atlas (TCGA) database according to 510 thyroid cancer tissues and 58 normal thyroid tissues. By using R package edgeR, differentially expressed RNAs were obtained. Also, an overall survival model was established based on Cox regression and clinical data then testified by Kaplan-Meier plot, receiver operating characteristic (ROC)-curve and C-index analysis. We investigated the co-expressed genes with lncRNAs involved in the prognostic model, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted R package clusterProfile. RESULTS A total of 352 lncRNAs were identified as differentially expressed in thyroid carcinoma, and an overall survival model consisting of 8 signature lncRNAs was proposed (ROC=0.862, C-index=0.893, P<0.05), 3 of which (DOCK9-DT, FAM111A-DT, and LINC01736) represent co-expressed mRNAs. However, as an oncogene, only FAM111A-DT increased the prognostic risk in thyroid carcinoma. Furthermore, we found differential genes LINC01016, LHX1-DT, IGF2-AS, ND MIR1-1HG-AS1, significantly related to lymph node metastasis (P<0.05). CONCLUSIONS In this study, we clarified the differential lncRNA expression profiles which were related to the tumorigenesis and prognosis in thyroid carcinoma. Our results provide new rationale and understandings to the pathogenesis and regulatory mechanisms of thyroid carcinoma.
甲状腺癌是一种发病率和死亡率都很高的恶性肿瘤。遗传改变在甲状腺癌的发病机制中起着关键作用,其中长链非编码 RNA(lncRNA)已被确定为至关重要的因素。本研究旨在探讨 lncRNA 表达谱在甲状腺癌中的生物学功能。
根据 510 例甲状腺癌组织和 58 例正常甲状腺组织,从癌症基因组图谱(TCGA)数据库中获取 lncRNA 表达谱。使用 R 包 edgeR 获得差异表达的 RNA。还基于 Cox 回归和临床数据建立了一个总生存模型,然后通过 Kaplan-Meier 图、接收者操作特征(ROC)-曲线和 C 指数分析进行验证。我们调查了与参与预后模型的 lncRNA 有共表达的基因,以及基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析。
共鉴定出 352 个在甲状腺癌中差异表达的 lncRNA,提出了一个由 8 个特征 lncRNA 组成的总生存模型(ROC=0.862,C 指数=0.893,P<0.05),其中 3 个(DOCK9-DT、FAM111A-DT 和 LINC01736)代表共表达的 mRNAs。然而,作为一种癌基因,只有 FAM111A-DT 增加了甲状腺癌的预后风险。此外,我们发现差异基因 LINC01016、LHX1-DT、IGF2-AS、ND MIR1-1HG-AS1 与淋巴结转移显著相关(P<0.05)。
本研究阐明了与甲状腺癌发生和预后相关的差异 lncRNA 表达谱。我们的研究结果为甲状腺癌的发病机制和调控机制提供了新的依据和认识。