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在罕见恶性瘤中发现生物标志物:开发RDEB-cSCC的miRNA签名

Roland Zauner¹, Monika Wimmer¹, Sabine Atzmueller²

¹EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology & Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.

|July 14, 2023

概括

机器学习模型使用miRNA签名准确地检测了衰退性缩性表皮溶解牛 (RDEB) 患者的罕见皮肤状细胞癌 (cSCC). 这种方法利用公共数据来改善早期瘤检测和临床可行性.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
生物信息学是一种生物信息学.

背景情况:

机器学习 (ML) 有助于瘤生物标记物识别,但由于患者数据有限,它与罕见癌症作斗争.
衰退性缩性表皮溶解 (RDEB) 患者面临着侵袭性皮肤状细胞癌 (cSCC) 的高风险,需要早期检测.
微RNAs (miRNAs) 显示出作为液体活检标记物用于非侵入性癌症检测的前景.

研究的目的:

在RDEB中对miRNA签名进行表征,以潜在的瘤检测.
通过使用TCGA数据分析miRNA与其他瘤类型的样本相似性,以克服RDEB样本稀缺性.
开发和验证基于ML的RDEB-cSCC检测的预测模型.

主要方法:

分析了来自RDEB初级细胞的miRNA表达特征,并将其与TCGA瘤数据进行了比较.
训练有素的弹性净逻辑回归模型使用33,10和3 miRNAs基于头部和部状细胞癌 (HN-SCC) 数据.
在独立的HN-SCC数据集,基于RDEB细胞的miRNA-Seq数据和RDEB外体上验证了模型性能.

主要成果:

确定了RDEB-SCC和HN-SCC之间的显著miRNA相似性,使模型训练成为可能.
在包括RDEB外体在内的数据集中实现了高预测性能 (AUC-ROC 83-100%),证明了临床潜力.
开发了三种不同的ML模型,具有不同的miRNA复杂性,所有模型都显示出强大的诊断能力.

结论:

使用ML和公开可用的数据,用于RDEB-cSCC检测的诊断miRNA签名是可行的.
开发的模型显示高准确性预测瘤从基于细胞的数据和外体.
这种方法可以改善与RDEB相关的cSCC的早期检测,促进及时干预.

关键词:

生物标志物生物标志物皮肤溶解牛皮质的表皮质.外基因组是外基因组的组成部分.这是一个小RNARNA.状细胞癌是状细胞癌.

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...