Abstract
Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with short survival time. Unbalanced competing endogenous RNAs (ceRNAs) have been shown to participate in the tumor pathogenesis and served as biomarkers for the clinical prognosis. However, the comprehensive analyses of the ceRNA network in the prognosis of MPM are still rarely reported. In this study, we obtained the transcriptome data of the MPM and the normal samples from TCGA, EGA, and GEO databases and identified the differentially expressed (DE) mRNAs, lncRNAs, and miRNAs. The functions of the prognostic genes and the overlapped DEmRNAs were further annotated by the multiple enrichment analyses. Then, the targeting relationships among lncRNA–miRNA and miRNA–mRNA were predicted and calculated, and a prognostic ceRNA regulatory network was established. We included the prognostic 73 mRNAs and 13 miRNAs and 26 lncRNAs into the ceRNA network. Moreover, 33 mRNAs, three miRNAs, and seven lncRNAs were finally associated with prognosis, and a model including seven mRNAs, two lincRNAs, and some clinical factors was finally established and validated by two independent cohorts, where CDK6 and SGMS1-AS1 were significant to be independent prognostic factors. In addition, the identified co-expressed modules associated with the prognosis were overrepresented in the ceRNA network. Multiple enrichment analyses showed the important roles of the extracellular matrix components and cell division dysfunction in the invasion of MPM potentially. In summary, the prognostic ceRNA network of MPM was established and analyzed for the first time and these findings shed light on the function of ceRNAs and revealed the potential prognostic and therapeutic biomarkers of MPM.
Highlights
Malignant pleural mesothelioma (MPM), which is mainly associated with the asbestos exposure and derived from the pleural or peritoneal mesothelial cell surfaces, is an aggressive tumor with very poor prognosis [1]
This study provides new insights on the biological functions related to the lncRNA in MPM patients and the additional biomarkers for the prognosis of MPM
According to the results of the differential expression gene (DEG), the patients were clearly clustered into two groups, indicating that the overall gene expression patterns are significantly different in the two groups (Figures 1A,B)
Summary
Malignant pleural mesothelioma (MPM), which is mainly associated with the asbestos exposure and derived from the pleural or peritoneal mesothelial cell surfaces, is an aggressive tumor with very poor prognosis (median survival time < 12 months after diagnosis) [1]. The number of patients has been increasing in recent years, especially in developing countries, which leads to ca. It is difficult to differentially diagnose MPM, since inclusion of more biomarkers based on the latest research would likely increase the accuracy and efficiency of prognosis. Some ceRNAs have been shown to be valuable targets for the treatment and prognosis of multiple cancers [7, 8]. There are few studies focused on the function of ceRNA networks in MPM. Some recent studies implicated that noncoding RNA (ncRNA) dysfunction is closely associated with the properties of MPM cells [11,12,13]. It is highly likely that certain ceRNA networks may be involved in the pathogenesis of MPM
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