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Identification of candidate biomarkers and pathways associated with SCLC by bioinformatics analysis.
Wen, Pushuai; Chidanguro, Tungamirai; Shi, Zhuo; Gu, Huanyu; Wang, Nan; Wang, Tongmei; Li, Yuhong; Gao, Jing.
Afiliación
  • Wen P; Department of Pathophysiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Chidanguro T; Department of Pathophysiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Shi Z; Department of Anatomy, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Gu H; Department of Pathophysiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Wang N; Department of Pathophysiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Wang T; Department of Pathophysiology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Li Y; Department of Ultrasonography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
  • Gao J; Department of Ultrasonography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
Mol Med Rep ; 18(2): 1538-1550, 2018 Aug.
Article en En | MEDLINE | ID: mdl-29845250
Small cell lung cancer (SCLC) is one of the highly malignant tumors and a serious threat to human health. The aim of the present study was to explore the underlying molecular mechanisms of SCLC. mRNA microarray datasets GSE6044 and GSE11969 were downloaded from Gene Expression Omnibus database, and the differentially expressed genes (DEGs) between normal lung and SCLC samples were screened using GEO2R tool. Functional and pathway enrichment analyses were performed for common DEGs using the DAVID database, and the protein­protein interaction (PPI) network of common DEGs was constructed by the STRING database and visualized with Cytoscape software. In addition, the hub genes in the network and module analysis of the PPI network were performed using CentiScaPe and plugin Molecular Complex Detection. Finally, the mRNA expression levels of hub genes were validated in the Oncomine database. A total of 150 common DEGs with absolute fold­change >0.5, including 66 significantly downregulated DEGs and 84 upregulated DEGs were obtained. The Gene Ontology term enrichment analysis suggested that common upregulated DEGs were primarily enriched in biological processes (BPs), including 'cell cycle', 'cell cycle phase', 'M phase', 'cell cycle process' and 'DNA metabolic process'. The common downregulated genes were significantly enriched in BPs, including 'response to wounding', 'positive regulation of immune system process', 'immune response', 'acute inflammatory response' and 'inflammatory response'. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that the common downregulated DEGs were primarily enriched in the 'complement and coagulation cascades' signaling pathway; the common upregulated DEGs were mainly enriched in 'cell cycle', 'DNA replication', 'oocyte meiosis' and the 'mismatch repair' signaling pathways. From the PPI network, the top 10 hub genes in SCLC were selected, including topoisomerase IIα, proliferating cell nuclear antigen, replication factor C subunit 4, checkpoint kinase 1, thymidylate synthase, minichromosome maintenance protein (MCM) 2, cell division cycle (CDC) 20, cyclin dependent kinase inhibitor 3, MCM3 and CDC6, the mRNA levels of which are upregulated in Oncomine SCLC datasets with the exception of MCM2. Furthermore, the genes in the significant module were enriched in 'cell cycle', 'DNA replication' and 'oocyte meiosis' signaling pathways. Therefore, the present study can shed new light on the understanding of molecular mechanisms of SCLC and may provide molecular targets and diagnostic biomarkers for the treatment and early diagnosis of SCLC.
Asunto(s)
Biomarcadores de Tumor/genética; Regulación Neoplásica de la Expresión Génica; Redes Reguladoras de Genes; Neoplasias Pulmonares/genética; Carcinoma Pulmonar de Células Pequeñas/genética; Biomarcadores de Tumor/metabolismo; Proteínas Cdc20/genética; Proteínas Cdc20/metabolismo; Proteínas de Ciclo Celular/genética; Proteínas de Ciclo Celular/metabolismo; Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/genética; Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo; Biología Computacional/métodos; Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/genética; Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/metabolismo; ADN-Topoisomerasas de Tipo II/genética; ADN-Topoisomerasas de Tipo II/metabolismo; Bases de Datos Genéticas; Perfilación de la Expresión Génica; Ontología de Genes; Humanos; Neoplasias Pulmonares/diagnóstico; Neoplasias Pulmonares/metabolismo; Neoplasias Pulmonares/patología; Componente 2 del Complejo de Mantenimiento de Minicromosoma/genética; Componente 2 del Complejo de Mantenimiento de Minicromosoma/metabolismo; Componente 3 del Complejo de Mantenimiento de Minicromosoma/genética; Componente 3 del Complejo de Mantenimiento de Minicromosoma/metabolismo; Anotación de Secuencia Molecular; Proteínas Nucleares/genética; Proteínas Nucleares/metabolismo; Proteínas de Unión a Poli-ADP-Ribosa/genética; Proteínas de Unión a Poli-ADP-Ribosa/metabolismo; Antígeno Nuclear de Célula en Proliferación/genética; Antígeno Nuclear de Célula en Proliferación/metabolismo; Mapeo de Interacción de Proteínas; Proteína de Replicación C/genética; Proteína de Replicación C/metabolismo; Carcinoma Pulmonar de Células Pequeñas/diagnóstico; Carcinoma Pulmonar de Células Pequeñas/metabolismo; Carcinoma Pulmonar de Células Pequeñas/patología; Programas Informáticos; Timidilato Sintasa/genética; Timidilato Sintasa/metabolismo; Transcriptoma
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / Redes Reguladoras de Genes / Carcinoma Pulmonar de Células Pequeñas / Neoplasias Pulmonares Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Idioma: En Revista: Mol Med Rep Año: 2018 Tipo del documento: Article Pais de publicación: Grecia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / Redes Reguladoras de Genes / Carcinoma Pulmonar de Células Pequeñas / Neoplasias Pulmonares Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Idioma: En Revista: Mol Med Rep Año: 2018 Tipo del documento: Article Pais de publicación: Grecia