甲状腺乳头癌的综合转录组分析：与肿瘤进展相关的潜在生物标志物。

Comprehensive transcriptomic analysis of papillary thyroid cancer: potential biomarkers associated with tumor progression.

机构信息

Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.

Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland.

出版信息

J Endocrinol Invest. 2020 Jul;43(7):911-923. doi: 10.1007/s40618-019-01175-7. Epub 2020 Jan 21.

DOI:10.1007/s40618-019-01175-7

PMID:31965517

Abstract

PURPOSE

Identification of stage-specific prognostic/predictive biomarkers in papillary thyroid carcinoma (PTC) could lead to its more efficient clinical management. The main objective of this study was to characterize the stage-specific deregulation in genes and miRNA expression in PTC to identify potential prognostic biomarkers.

METHODS

495 RNASeq and 499 miRNASeq PTC samples (stage I-IV) as well as, respectively, 56 and 57 normal samples were retrieved from The Cancer Genome Atlas (TCGA). Differential expression analysis was performed using DESeq 2 to identify deregulation of genes and miRNAs between sequential stages. To identify the minority of patients who progress to higher stages, we performed clustering analysis on stage I RNASeq data. An independent PTC RNASeq data set (BioProject accession PRJEB11591) was also used for the validation of the results.

RESULTS

LTF and PLA2R1 were identified as two promising biomarkers down-regulated in a subgroup of stage I (both in TCGA and in the validation data set) and in the majority of stage IV of PTC (in TCGA data set). hsa-miR-205, hsa-miR-509-2, hsa-miR-514-1 and hsa-miR-514-2 were also detected as up-regulated miRNAs in both PTC patients with stage I and stage III. Hierarchical clustering of stage I samples showed substantial heterogeneity in the expression pattern of PTC indicating the necessity of categorizing stage I patients based on the expressional alterations of specific biomarkers.

CONCLUSION

Stage I PTC patients showed large amount of expressional heterogeneity. Therefore, risk stratification based on the expressional alterations of candidate biomarkers could be an important step toward personalized management of these patients.

摘要

目的

鉴定甲状腺乳头状癌（PTC）中具有特定分期预后/预测作用的生物标志物，有助于更有效地进行临床管理。本研究的主要目的是分析 PTC 中基因和 miRNA 表达的特定分期失调情况，以鉴定潜在的预后生物标志物。

方法

从癌症基因组图谱（TCGA）中检索了 495 例 RNA-seq 和 499 例 miRNA-seq PTC 样本（I-IV 期），以及分别 56 例和 57 例正常样本。采用 DESeq2 进行差异表达分析，以鉴定各连续分期之间基因和 miRNA 的失调情况。为了鉴定少数进展为更高分期的患者，我们对 I 期 RNA-seq 数据进行聚类分析。还使用了另一个独立的 PTC RNA-seq 数据集（生物项目注册号 PRJEB11591）来验证结果。

结果

LTF 和 PLA2R1 被鉴定为在 TCGA 和验证数据集的 I 期亚组以及 TCGA 数据集的大多数 IV 期 PTC 中下调的两种有前途的生物标志物。hsa-miR-205、hsa-miR-509-2、hsa-miR-514-1 和 hsa-miR-514-2 也被鉴定为 I 期和 III 期 PTC 患者中上调的 miRNA。I 期样本的层次聚类显示 PTC 的表达模式存在很大的异质性，表明有必要根据特定生物标志物的表达变化对 I 期患者进行分类。