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甲状腺乳头状癌中的 microRNA 谱分析。

MicroRNA Profiling in Papillary Thyroid Cancer.

机构信息

Department of Medicine and Oncology, Faculty of Medicine, Semmelweis University, 1083 Budapest, Hungary.

SE HUN-REN-TKI ENDOMOLPAT Research Group, 1085 Budapest, Hungary.

出版信息

Int J Mol Sci. 2024 Aug 29;25(17):9362. doi: 10.3390/ijms25179362.

Abstract

Genetic alterations are well known to be related to the pathogenesis and prognosis of papillary thyroid carcinoma (PTC). Some miRNA expression dysregulations have previously been described in the context of cancer development including thyroid carcinoma. In our study, we performed original molecular diagnostics on tissue samples related to our own patients. We aimed to identify all dysregulated miRNAs in potential association with PTC development via sequencing much higher numbers of control-matched PTC tissue samples and analyzing a wider variety of miRNA types than previous studies. We analyzed the expression levels of 2656 different human miRNAs in the context of 236 thyroid tissue samples (118 tumor and control pairs) related to anonymized PTC cases. Also, KEGG pathway enrichment analysis and GO framework analysis were used to establish the links between miRNA dysregulation and certain biological processes, pathways of signaling, molecular functions, and cellular components. A total of 30 significant differential miRNA expressions with at least ±1 log fold change were found related to PTC including, e.g., miR-551b, miR-146b, miR-221, miR-222, and miR-375, among others, being highly upregulated, as well as miR-873 and miR-204 being downregulated. In addition, we identified miRNA patterns in vast databases (KEGG and GO) closely similar to that of PTC including, e.g., miRNA patterns of prostate cancer, HTLV infection, HIF-1 signaling, cellular responses to growth factor stimulus and organic substance, and negative regulation of gene expression. We also found 352 potential associations between certain miRNA expressions and states of clinicopathological variables. Our findings-supported by the largest case number of original matched-control PTC-miRNA relation research-suggest a distinct miRNA expression profile in PTC that could contribute to a deeper understanding of the underlying molecular mechanisms promoting the pathogenesis of the disease. Moreover, significant miRNA expression deviations and their signaling pathways in PTC presented in our study may serve as potential biomarkers for PTC diagnosis and prognosis or even therapeutic targets in the future.

摘要

遗传改变与甲状腺乳头状癌(PTC)的发病机制和预后密切相关。先前已经在癌症发展的背景下描述了一些 miRNA 表达失调,包括甲状腺癌。在我们的研究中,我们对与我们自己的患者相关的组织样本进行了原始的分子诊断。我们旨在通过对更多数量的配对 PTC 组织样本进行测序,并分析比以前的研究更广泛的 miRNA 类型,来识别与 PTC 发展潜在相关的所有失调 miRNA。我们分析了 2656 种不同的人类 miRNA 在 236 份与 PTC 病例相关的甲状腺组织样本(118 个肿瘤和对照配对)中的表达水平。此外,KEGG 途径富集分析和 GO 框架分析用于建立 miRNA 失调与某些生物学过程、信号通路、分子功能和细胞成分之间的联系。我们发现与 PTC 相关的 30 个具有至少±1 log 倍变化的显著差异 miRNA 表达,包括 miR-551b、miR-146b、miR-221、miR-222 和 miR-375 等高度上调,以及 miR-873 和 miR-204 下调。此外,我们在庞大的数据库(KEGG 和 GO)中鉴定了与 PTC 非常相似的 miRNA 模式,包括前列腺癌、HTLV 感染、HIF-1 信号、细胞对生长因子刺激和有机物质的反应以及基因表达的负调控等 miRNA 模式。我们还发现某些 miRNA 表达与临床病理变量状态之间存在 352 种潜在关联。我们的发现——基于最大数量的原始配对对照 PTC-miRNA 关系研究——表明 PTC 存在明显的 miRNA 表达谱,这可能有助于深入了解促进疾病发病机制的潜在分子机制。此外,我们研究中 PTC 中存在显著的 miRNA 表达偏差及其信号通路,可能作为 PTC 诊断和预后的潜在生物标志物,甚至是未来的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36c0/11395536/9882872864ec/ijms-25-09362-g001.jpg

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