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黑色素瘤进展中的分子标志物:肿瘤性 vs. 良性痣中 miRNA 基因亚型表达的研究。

Molecular Markers in Melanoma Progression: A Study on the Expression of miRNA Gene Subtypes in Tumoral vs. Benign Nevi.

机构信息

Doctoral School, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.

Department of Plastic Surgery, "Pius Brinzeu" Timis County Emergency Clinical Hospital, 300723 Timisoara, Romania.

出版信息

Curr Oncol. 2024 May 17;31(5):2881-2894. doi: 10.3390/curroncol31050220.

Abstract

This study investigates the differential expression of miRNA gene subtypes in tumoral versus benign nevi in individuals with melanoma, aiming to identify clinically significant correlations that could serve as reliable markers for assessing tumor stage and progression. Conducted between 2019 and 2022, this descriptive, quantitative observational research analyzed 90 formalin-fixed paraffin-embedded (FFPE) samples from the Pius Brinzeu County Emergency Clinical Hospital, Timisoara, including 45 samples of advanced-stage melanoma and 45 samples of pigmented nevi. miRNA purification and analysis were performed using the miRNeasy Kit and the Human Cancer PathwayFinder miScript miRNA PCR Array, with statistical analysis (including logistic regression) to determine associations with cancer staging, such as high Breslow index risk, number of mitoses, and vascular invasion. After the analysis and comparison of 180 miRNA gene subtypes, we selected 10 of the most upregulated and 10 most downregulated genes. The results revealed that hsa-miR-133b, hsa-miR-335-5p, hsa-miR-200a-3p, and hsa-miR-885-5p were significantly upregulated in melanoma samples, with fold changes ranging from 1.09 to 1.12. Conversely, hsa-miR-451a and hsa-miR-29b-3p showed notable downregulation in melanoma, with fold changes of 0.90 and 0.92, respectively. Additionally, logistic regression analysis identified hsa-miR-29b-3p (OR = 2.51) and hsa-miR-200a-3p (OR = 2.10) as significantly associated with an increased risk of a high Breslow index, while hsa-miR-127-3p and hsa-miR-451a were associated with a reduced risk. Conclusively, this study underscores the significant alterations in miRNA expression in melanoma compared to benign nevi and highlights the potential of specific miRNAs as biomarkers for melanoma progression. The identification of miRNAs with significant associations to melanoma characteristics suggests their utility in developing non-invasive, cost-effective diagnostic tools and in guiding therapeutic decisions, potentially improving patient outcomes in melanoma management.

摘要

本研究旨在探讨黑色素瘤患者肿瘤性与良性痣之间 miRNA 基因亚型的差异表达,旨在确定具有临床意义的相关性,作为评估肿瘤分期和进展的可靠标志物。这项描述性、定量观察性研究于 2019 年至 2022 年期间在蒂米什瓦拉皮斯·布林泽乌县紧急临床医院进行,分析了 90 例福尔马林固定石蜡包埋(FFPE)样本,包括 45 例晚期黑色素瘤样本和 45 例色素痣样本。使用 miRNeasy 试剂盒和 Human Cancer PathwayFinder miScript miRNA PCR Array 进行 miRNA 纯化和分析,采用统计学分析(包括逻辑回归)来确定与癌症分期相关的关联,如高 Breslow 指数风险、有丝分裂数和血管浸润。在对 180 种 miRNA 基因亚型进行分析和比较后,我们选择了 10 种上调最明显和 10 种下调最明显的基因。结果表明,hsa-miR-133b、hsa-miR-335-5p、hsa-miR-200a-3p 和 hsa-miR-885-5p 在黑色素瘤样本中显著上调,倍数变化范围为 1.09 至 1.12。相反,hsa-miR-451a 和 hsa-miR-29b-3p 在黑色素瘤中显著下调,倍数变化分别为 0.90 和 0.92。此外,逻辑回归分析确定 hsa-miR-29b-3p(OR=2.51)和 hsa-miR-200a-3p(OR=2.10)与高 Breslow 指数风险增加显著相关,而 hsa-miR-127-3p 和 hsa-miR-451a 与风险降低相关。综上所述,本研究强调了黑色素瘤与良性痣之间 miRNA 表达的显著改变,并突出了特定 miRNA 作为黑色素瘤进展生物标志物的潜力。鉴定与黑色素瘤特征具有显著相关性的 miRNA 表明,它们可用于开发非侵入性、具有成本效益的诊断工具,并指导治疗决策,有可能改善黑色素瘤管理中的患者结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa7/11120387/8706526b9fce/curroncol-31-00220-g001.jpg

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