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文章:

亚洲人群子宫内膜癌中的MicroRNA图谱:揭示亚型特异性标志物

MicroRNA Landscape in Endometrial Carcinomas in an Asian population: Unraveling Subtype-Specific Signatures

原文发布日期:2 November 2023

DOI: 10.3390/cancers15215260

类型: Article

开放获取: 是

 

英文摘要:

MicroRNAs (MiRNAs) are small, non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We analyzed the differential expression of miRNAs in 119 endometrial carcinomas, measuring their expression in histological subtypes, molecular subtypes, and tumors withCTNNB1mutations. Tumors were subdivided into histological and molecular subtypes as defined by The Cancer Genome Atlas. The expression levels of 352 miRNAs were quantified using the PanoramiR panel. Mir-449a, mir-449b-5p, and mir-449c-5p were the top three miRNAs showing increased expression in both endometrioid and de-differentiated carcinomas but were not significantly increased in serous and clear cell carcinomas. The miRNAs with the most increased expression in serous and clear cell carcinomas were miR-9-3p and miR-375, respectively. We also identified 62 differentially expressed miRNAs among different molecular subtypes. Using sequential forward selection, we built subtype classification models for some molecular subtypes of endometrial carcinoma, comprising 5 miRNAs for MMR-deficient tumors, 10 miRNAs for p53-mutated tumors, and 3 miRNAs forCTNNB1-mutated tumors, with areas under curves of 0.75, 0.85, and 0.78, respectively. Our findings confirm the differential expression of miRNAs between various endometrial carcinoma subtypes and may have implications for the development of diagnostic and prognostic tools.

 

摘要翻译: 

MicroRNAs(MiRNAs)是一类小型非编码RNA分子,在RNA沉默和基因表达的转录后调控中发挥作用。本研究分析了119例子宫内膜癌中miRNAs的差异表达,检测了其在组织学亚型、分子亚型以及携带CTNNB1突变肿瘤中的表达水平。根据癌症基因组图谱标准,将肿瘤划分为组织学亚型和分子亚型。通过PanoramiR检测板对352种miRNAs的表达水平进行定量分析。结果显示,mir-449a、mir-449b-5p和mir-449c-5p在子宫内膜样癌和去分化癌中表达上调最为显著,而在浆液性癌和透明细胞癌中未见明显升高。浆液性癌中表达上调最显著的miRNA为miR-9-3p,透明细胞癌中则为miR-375。在不同分子亚型间,我们共鉴定出62种差异表达的miRNAs。通过顺序前向选择法,我们构建了子宫内膜癌特定分子亚型的分类模型:错配修复缺陷型肿瘤包含5种miRNAs,p53突变型肿瘤包含10种miRNAs,CTNNB1突变型肿瘤包含3种miRNAs,其曲线下面积分别为0.75、0.85和0.78。本研究证实了miRNAs在不同子宫内膜癌亚型间的差异表达特征,可能为诊断和预后工具的开发提供新思路。

 

原文链接:

MicroRNA Landscape in Endometrial Carcinomas in an Asian population: Unraveling Subtype-Specific Signatures

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