Liyanarachchi Sandya, Li Wei, Yan Pearlly, Bundschuh Ralf, Brock Pamela, Senter Leigha, Ringel Matthew D, de la Chapelle Albert, He Huiling
Human Cancer Genetics Program and Department of Cancer Biology and Genetics (S.L., W.L., P.B., L.S., A.d.l.C., H.H.) and Departments of Internal Medicine (P.Y., P.B., L.S., M.D.R.) and Physics (R.B.), The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210.
J Clin Endocrinol Metab. 2016 Nov;101(11):4005-4013. doi: 10.1210/jc.2016-1991. Epub 2016 Jul 26.
Long noncoding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood.
To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics.
We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters. The 2 most significantly dysregulated lncRNAs were studied in an Ohio PTC cohort (n = 109) and in PTC data (n = 497) from The Cancer Genome Atlas.
A combination of laboratory-based studies and computational analysis using clinical data and samples and a publically available database.
Correlation between expression values and clinical parameters.
We identified 218 lncRNAs showing differential expression in PTC (fold change ≥ 2.0, P < .01). Significant correlation was observed between the expression of 2 lncRNAs (XLOC_051122 and XLOC_006074) and 1) lymph node metastasis (N stage) and 2) BRAF(V600E) mutation. Among patients with wild-type BRAF, the expression of these 2 lncRNAs showed significantly higher levels in the patients with lymph node metastasis. In silico analysis of these lncRNAs pinpointed cell movement and cellular growth and proliferation as targeted functions.
Comprehensive expression screening identified 2 novel lncRNAs associated with risk factors of adverse prognosis in PTC patients. These lncRNAs may be novel players in PTC carcinogenesis.
长链非编码RNA（lncRNA）可调节病理过程，但其在甲状腺乳头状癌（PTC）中的潜在作用尚不清楚。
分析PTC中转录失调的lncRNA，并鉴定与临床病理特征相关的lncRNA。
我们对12对PTC肿瘤及其配对的癌旁组织进行了RNA测序，并将lncRNA的表达与临床参数进行关联分析。在俄亥俄州的PTC队列（n = 109）以及来自癌症基因组图谱的PTC数据（n = 497）中研究了2个失调最显著的lncRNA。
结合基于实验室的研究以及使用临床数据、样本和公开可用数据库进行的计算分析。
表达值与临床参数之间的相关性。
我们鉴定出218个在PTC中表现出差异表达的lncRNA（倍数变化≥2.0，P <.01）。观察到2个lncRNA（XLOC_051122和XLOC_006074）的表达与1）淋巴结转移（N分期）和2）BRAF（V600E）突变之间存在显著相关性。在BRAF野生型患者中，这2个lncRNA的表达在有淋巴结转移的患者中显著更高。对这些lncRNA的计算机分析确定细胞运动以及细胞生长和增殖为靶向功能。
全面的表达筛选鉴定出2个与PTC患者不良预后风险因素相关的新型lncRNA。这些lncRNA可能是PTC致癌过程中的新参与者。
