Tan Gideon Ze Lin, Leong Sai Mun, Jin Yu, Kuick Chik Hong, Chee Jeremy Joon Keat, Low San Zeng, Ding Ling-Wen, Cheng He, Lim Diana, Hue Susan Swee-Shan
Department of Pathology, National University Hospital, Singapore 118177, Singapore.
Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
Cancers (Basel). 2023 Nov 2;15(21):5260. doi: 10.3390/cancers15215260.
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 with mutations. 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 for -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.
微小RNA(miRNA)是一类小的非编码RNA分子,在RNA沉默和基因表达的转录后调控中发挥作用。我们分析了119例子宫内膜癌中miRNA的差异表达,检测了它们在组织学亚型、分子亚型以及有突变的肿瘤中的表达情况。肿瘤根据癌症基因组图谱的定义被细分为组织学和分子亚型。使用PanoramiR检测板对352种miRNA的表达水平进行了定量。Mir-449a、mir-449b-5p和mir-449c-5p是在子宫内膜样癌和去分化癌中表达均增加的前三种miRNA,但在浆液性癌和透明细胞癌中未显著增加。在浆液性癌和透明细胞癌中表达增加最多的miRNA分别是miR-9-3p和miR-375。我们还在不同分子亚型中鉴定出62种差异表达的miRNA。通过逐步向前选择,我们构建了子宫内膜癌某些分子亚型的分类模型,其中错配修复缺陷肿瘤包含5种miRNA,p53突变肿瘤包含10种miRNA,β-连环蛋白突变肿瘤包含3种miRNA,曲线下面积分别为0.75、0.85和0.78。我们的研究结果证实了不同子宫内膜癌亚型之间miRNA的差异表达,可能对诊断和预后工具的开发具有重要意义。