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

甲状腺乳头状癌的综合转录组学分析: 与肿瘤进展相关的潜在生物标志物。

  • 影响因子:2.82
  • DOI:10.1007/s40618-019-01175-7
  • 作者列表:"Hosseinkhan N","Honardoost M","Blighe K","Moore CBT","Khamseh ME
  • 发表时间:2020-01-21
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: 甲状腺乳头状癌 (PTC) 中阶段特异性预后/预测生物标志物的鉴定可能导致其更有效的临床管理。本研究的主要目的是表征 PTC 中基因和 miRNA 表达的阶段特异性失调,以确定潜在的预后生物标志物。 方法: 从癌症基因组图谱 (TCGA) 中分别检索到 495 份 RNASeq 和 499 份 miRNASeq PTC 样本 (I-IV 期) 以及 56 份和 57 份正常样本。使用 DESeq 2 进行差异表达分析,以鉴定序列阶段之间的基因和 miRNAs 的失调。为了确定少数进展到更高阶段的患者,我们对 I 期 RNASeq 数据进行了聚类分析。独立的 PTC RNASeq 数据集 (BioProject accession PRJEB11591) 也用于结果的验证。 结果: LTF 和 PLA2R1 被确定为两个有希望的生物标志物,在 I 期亚组中下调 (在 TCGA 和验证数据集中) 并且在 PTC 的大部分 IV 期 (在 TCGA 数据集中)。 hsa-miR-205,hsa-miR-509-2,在 I 期和 III 期 PTC 患者中也检测到 hsa-miR-514-1 和 hsa-miR-514-2 作为上调的 miRNAs。I 期样本的分层聚类显示了 PTC 表达模式的实质性异质性,表明根据特定生物标志物的表达改变对 I 期患者进行分类的必要性。 结论: ⅰ 期 PTC 患者表现为大量的表达异质性。因此,基于候选生物标志物表达改变的风险分层可能是这些患者个性化管理的重要一步。

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相关文献
影响因子:2.13
发表时间:2020-01-02
DOI:10.1093/ajcp/aqz145
作者列表:["Travaglino A","Pace M","Varricchio S","Insabato L","Giordano C","Picardi M","Pane F","Staibano S","Mascolo M"]

METHODS:OBJECTIVES:To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS:Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS:Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS:Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.

翻译标题与摘要 下载文献
影响因子:2.24
发表时间:2020-01-08
DOI:10.1007/s00268-019-05337-9
作者列表:["Lee, Inhwa","Kim, Hyeung Kyoo","Soh, Euy Young","Lee, Jeonghun"]

METHODS:Background Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. Methods Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. Results In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. Conclusions The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.

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翻译标题与摘要 下载文献
影响因子:2.69
发表时间:2020-01-29
DOI:10.1016/j.bbrc.2019.11.047
作者列表:["Zhang Z","Xu T","Qin W","Huang B","Chen W","Li S","Li J"]

METHODS::PTPN2 is one of the members of the protein Tyrosine Phosphatases (PTPs) family. To explore the promotive effect of upregulated PTPN2 induced by inflammatory response or oxidative stress on the progression of thyroid cancer. PTPN2 level in thyroid cancer tissues and cell lines was detected. Kaplan-Meier method was applied for evaluating the prognostic value of PTPN2 in thyroid cancer patients. After stimulation of inflammatory response (treatment of IFN-γ and TNF-α), or oxidative stress (treatment of H2O2), protein level of PTPN2 in K1 cells was measured by Western blot. Regulatory effects of PTPN2 on EdU-positive staining and Ki-67 positive cell ratio in K1 cells either with H2O2 stimulation or not were determined. PTPN2 was upregulated in thyroid cancer tissues and cell lines. Its level was higher in metastatic thyroid cancer patients than those of non-metastatic ones. High level of PTPN2 predicted worse prognosis of thyroid cancer. Treatment of either IFN-γ or TNF-α upregulated protein level of PTPN2 in K1 cells. Meanwhile, H2O2 stimulation upregulated PTPN2, which was reversed by NAC administration. With the stimulation of increased doses of H2O2, EdU-positive staining and Ki-67 positive cell ratio were dose-dependently elevated. Silence of PTPN2 attenuated proliferative ability and Ki-67 expression in K1 cells either with H2O2 stimulation or not. Inflammatory response or oxidative stress induces upregulation of PTPN2, thus promoting the progression of thyroid cancer.

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