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原发灶转移与非转移甲状腺乳头状癌基因表达谱的差异——是否存在?

Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma-Do They Exist?

机构信息

Nuclear Medicine and Endocrine Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-101 Gliwice, Poland.

Department of Genetic and Molecular Diagnostics of Cancer, Maria Sklodowska, Curie National Research Institute of Oncology Gliwice Branch, 44-101 Gliwice, Poland.

出版信息

Int J Mol Sci. 2020 Jun 29;21(13):4629. doi: 10.3390/ijms21134629.

Abstract

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A-U133, set B-HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: (most significant) and . However, when analyzed on an independent dataset by qPCR, the gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.

摘要

甲状腺乳头状癌(PTC)远处转移(M1)的分子机制尚不清楚。我们试图分析 PTC 原发肿瘤的基因表达谱,以寻找与 M1 状态相关的基因,并描述其分子功能。对 123 例患者(包括 36 例 M1 病例)进行了转录组寡核苷酸微阵列分析:(A 组-U133,B 组-HG 1.0 ST)在转录和基因组水平(limma,基因集富集分析(GSEA))。另外一组 63 例 PTC 患者(包括 9 例 M1 病例)用于通过 qPCR 验证结果。在数据集 A 的分析中,检测到 11 个在转移性和非转移性 PTC 之间表达差异显著的转录本。这些基因在微阵列数据集 B 上得到了验证。仅两个基因的差异表达得到了正向确认:(最显著)和。然而,当通过 qPCR 在独立数据集上进行分析时,基因在表达上没有差异。基因组分析主要显示免疫相关转录物之间的差异,表明原发性肿瘤内肿瘤免疫浸润或信号的潜在影响。如果存在转移性和非转移性 PTC 之间的基因表达谱差异,它们也很细微,可能仅在大型数据集上才能检测到。

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