Department of Occupational and Environmental Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea.
Department of Statistics, University of Michigan, Ann Arbor, MI, USA.
J Toxicol Environ Health A. 2020 Feb 1;83(3):126-134. doi: 10.1080/15287394.2020.1734891. Epub 2020 Mar 2.
Malignant pleural mesothelioma (MPM) is a type of cancer characterized by a short survival time and poor prognosis. Malignant pleural mesothelioma is most frequently associated with exposure to asbestos and other elongated mineral fibers. The aim of this study was to examine molecular differences between asbestos-exposed and non-exposed MPM patients and assess prognostic significances of molecular factors. Clinical and genetic data were downloaded from Cancer Genome Atlas. To identify the molecular differences, Significant Analysis of Microarray method was used. Prognostic significances of differentially expressed genes were confirmed by using Kaplan-Meier curve with the Log-Rank test. Although mRNAs did not exhibit any significant differences between the two patient groups, nine miRNAs were found to be down-regulated in the asbestos-exposed group. The top five pathways most relevant to the selected miRNAs were extracted through pathway enrichment analysis. Survival analysis revealed that high expression of only hsa-miR-98 was significantly associated with poor prognosis in patients with asbestos-exposed MPM. Evidence suggests that management of the aggressiveness and progression of asbestos-induced MPM may require high levels of hsa-miR-98 due to its tumor-suppressive role. This study might be helpful in enhancing our understanding of the biological mechanisms underlying asbestos-induced MPM and for acquiring greater insights into targeted therapy.: FDR: false discovery rate; MM: malignant mesothelioma; MPM: malignant pleural mesothelioma; mRNA: messenger RNA; miRNA: microRNA; SAM: significance analysis of microarrays; TCGA: the cancer genome atlas.
恶性胸膜间皮瘤(MPM)是一种生存期短、预后差的癌症。恶性胸膜间皮瘤最常与接触石棉和其他长纤维矿物质有关。本研究旨在研究石棉暴露和非暴露 MPM 患者之间的分子差异,并评估分子因素的预后意义。临床和遗传数据从癌症基因组图谱下载。为了识别分子差异,使用了显著分析微阵列方法。通过 Kaplan-Meier 曲线和对数秩检验来确认差异表达基因的预后意义。虽然两组患者之间的 mRNA 没有表现出任何显著差异,但发现 9 种 miRNA 在石棉暴露组中下调。通过途径富集分析提取与选定 miRNA 最相关的前 5 个途径。生存分析显示,只有 hsa-miR-98 的高表达与石棉暴露性 MPM 患者的预后不良显著相关。有证据表明,由于 hsa-miR-98 的肿瘤抑制作用,管理石棉诱导的 MPM 的侵袭性和进展可能需要高水平的 hsa-miR-98。本研究可能有助于加深我们对石棉诱导的 MPM 的生物学机制的理解,并为靶向治疗提供更深入的见解。