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对恶性胸膜间皮瘤患者血清中循环 microRNA 197-3p 的表观遗传学研究及曾接触石棉的工人。

Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos.

机构信息

Department of Medical Sciences, Laboratories of Cell Biology and Molecular Genetics, School of Medicine, University of Ferrara, 64B, Fossato di Mortara Street, 44121, Ferrara, Italy.

Department of Chemical, Pharmaceutical and Agricultural Sciences-DOCPAS, University of Ferrara, 44121, Ferrara, Italy.

出版信息

Sci Rep. 2023 Apr 20;13(1):6501. doi: 10.1038/s41598-023-33116-z.

Abstract

The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.

摘要

miRNAs 的表观遗传作用在生理和病理水平上都得到了确立。失调的 miRNAs 及其靶标似乎是创新抗癌疗法的有前途的方法。在我们之前的研究中,在接触过石棉的工人(WEA)的循环中检测到 miR-197-3p 失调。在此,对来自恶性胸膜间皮瘤(MPM)患者血清中的这种循环 miRNA 进行了表观遗传研究。使用 ddPCR 和 RT-qPCR 技术在 MPM(n=75)血清中定量 miR-197-3p,并与 WEA(n=75)和健康受试者(n=75)血清进行比较分析。在相关性研究中评估了临床病理特征、职业、非职业信息和总生存期(OS)。通过 ddPCR 分析,MPM 组 miR-197-3p 水平明显高于 WEA 组,分别为 981.7 和 525.01 个拷贝/µl。一致地,RT-qPCR 显示来自 MPM 的血清中 miR-197-3p 水平更高,平均拷贝/µl 为 603.7,而 WEA 组为 336.1 拷贝/µl。OS 数据与组织学亚型和胸膜切除术显著相关。循环 miR-197-3p 被提议作为 MPM 发病早期诊断的新的潜在生物标志物。事实上,miR-197-3p 的表观遗传研究以及胸部 X 光、计算机断层扫描和肺活量测定法可以提供相关信息,有助于对 MPM 进行早期和有效的诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f24/10119131/9023bec2fcb5/41598_2023_33116_Fig1_HTML.jpg

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