恶性胸膜间皮瘤中血清 DRAM1 mRNA、ARSA mRNA、hsa-miR-2053 和 lncRNA-RP1-86D1.3 轴表达的临床意义。

Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Department of Biomedical Research, Armed Forces College of Medicine, Cairo, Egypt.

出版信息

J Cell Biochem. 2019 Mar;120(3):3203-3211. doi: 10.1002/jcb.27586. Epub 2018 Oct 26.

DOI:10.1002/jcb.27586

PMID:30362153

Abstract

AIM AND BACKGROUND

Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.

METHODS

We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A ( ARSA) gene expression with their epigenetic regulators microRNA ( miR-2053) and long noncoding RNA ( lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.

RESULTS

The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.

CONCLUSION

Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.

摘要

目的和背景

恶性胸膜间皮瘤（MPM）是一种主要由慢性石棉暴露引起的致命癌症。在这项初步研究中，我们旨在评估血清 RNA 生物标志物面板的表达，探索其作为 MPM 诊断和预后生物标志物的临床应用价值。

方法

我们通过基于 DNA 损伤调节自噬调节剂 1（DRAM1）和芳基硫酸酯酶 A（ARSA）基因表达及其表观遗传调节剂 microRNA（miR-2053）和长非编码 RNA（lncRNA-RP1-86D1.3）的生物信息学分析，选择了一个 MPM 特异性 RNA 生物标志物面板。然后，对 60 名 MPM 患者、20 名慢性石棉暴露患者和 20 名健康志愿者的血清进行了定量实时聚合酶链反应（qPCR）验证。最后，评估了所选面板的预后能力。

结果

血清 DRAM1 信使 RNA（mRNA）、ARSA mRNA、hsa-miR-2053 和 lncRNA-RP1-86D1.3 的表达在 78.3%、90%、85%和 83.3%的 MPM 患者中呈阳性。RNA 生物标志物面板能够以高精度区分 MPM 患者和对照组，其联合敏感性达到 100%，可用于 MPM 的诊断。Kaplan-Meier 分析表明，hsa-miR-2053 是 MPM 的独立预后因素。