Molecular signatures identified by integrating gene expression and methylation in non-seminoma and seminoma of testicular germ cell tumours.

Mallik, Saurav; Qin, Guimin; Jia, Peilin; Zhao, Zhongming

Mallik, Saurav; Qin, Guimin; Jia, Peilin; Zhao, Zhongming.

Afiliación

Mallik S; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston , Houston, TX, USA.
Qin G; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston , Houston, TX, USA.
Jia P; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston , Houston, TX, USA.
Zhao Z; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston , Houston, TX, USA.

Epigenetics ; 16(2): 162-176, 2021.

Article en En | MEDLINE | ID: mdl-32615059

RESUMEN

Testicular germ cell tumours (TGCTs) are the most common cancer in young male adults (aged 15 to 40). Unlike most other cancer types, identification of molecular signatures in TGCT has rarely reported. In this study, we developed a novel integrative analysis framework to identify co-methylated and co-expressed genes [mRNAs and microRNAs (miRNAs)] modules in two TGCT subtypes: non-seminoma (NSE) and seminoma (SE). We first integrated DNA methylation and mRNA/miRNA expression data and then used a statistical method, CoMEx (Combined score of DNA Methylation and Expression), to assess differentially expressed and methylated (DEM) genes/miRNAs. Next, we identified co-methylation and co-expression modules by applying WGCNA (Weighted Gene Correlation Network Analysis) tool to these DEM genes/miRNAs. The module with the highest average Pearson's Correlation Coefficient (PCC) after considering all pair-wise molecules (genes/miRNAs) included 91 molecules. By integrating both transcription factor and miRNA regulations, we constructed subtype-specific regulatory networks for NSE and SE. We identified four hub miRNAs (miR-182-5p, miR-520b, miR-520c-3p, and miR-7-5p), two hub TFs (MYC and SP1), and two genes (RECK and TERT) in the NSE-specific regulatory network, and two hub miRNAs (miR-182-5p and miR-338-3p), five hub TFs (ETS1, HIF1A, HNF1A, MYC, and SP1), and three hub genes (CDH1, CXCR4, and SNAI1) in the SE-specific regulatory network. miRNA (miR-182-5p) and two TFs (MYC and SP1) were common hubs of NSE and SE. We further examined pathways enriched in these subtype-specific networks. Our study provides a comprehensive view of the molecular signatures and co-regulation in two TGCT subtypes.

Asunto(s)

MicroARNs; Neoplasias de Células Germinales y Embrionarias; Seminoma; Neoplasias Testiculares; Metilación de ADN; Expresión Génica; Perfilación de la Expresión Génica; Redes Reguladoras de Genes; Humanos; Masculino; MicroARNs/genética; Neoplasias de Células Germinales y Embrionarias/genética; Seminoma/genética; Neoplasias Testiculares/genética

Palabras clave

Testicular germ cell tumour; co-regulation network; methylation; microRNA; non-seminoma; seminoma

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Testiculares / Seminoma / Neoplasias de Células Germinales y Embrionarias / MicroARNs Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Epigenetics Asunto de la revista: GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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