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Distinct Molecular Mechanisms Analysis of Three Lung Cancer Subtypes Based on Gene Expression Profiles.

Journal of computational biology(2019)

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摘要
The purpose was to explore distinct molecular mechanisms of three lung cancer subtypes. GSE6044 microarray data downloaded from Gene Expression Omnibus (GEO) database were applied for identifying the differentially expressed genes (DEGs). Genetic global network was constructed to analyze the network annotation. The DEGs in the genetic global network related to small-cell lung carcinoma (SCLC), lung squamous cell carcinoma (SCC), and lung adenocarcinoma (AC) were screened. Protein-protein international networks of DEGs were constructed. Pathway enrichment analyses of DEGs in three subtypes were performed, followed by construction of interactional network among pathways. There were more DEGs screened in SCLC than in AC and SCC. The genetic global network with 341 genes and 1569 interaction edges was constructed. After annotating these DEGs into a protein interactional network, a total of 695 protein interactions related to these 36 DEGs were obtained. HSP90AA1 was the hub node with the highest degree of 81 in the annotation network. DEGs in SCLC and SCC were mainly enriched in some pathways, including cell cycle, DNA replication, and histidine metabolism; whereas DEGs in AC were enriched in complement and coagulation cascades, and extracellular matrix (ECM)-receptor interaction. Pathway interactional network was constructed with the hub node of a neuroactive ligand receptor interaction. The identified DEGs such as retinoid X receptor alpha (RXRA), cyclin-dependent kinase 2 (CDK2), histone deacetylase 2 (HDAC2), and KIT might be the target genes of lung cancer by participating in different pathways such as ECM-receptor interaction. Complement and coagulation cascades, and ECM-receptor interaction might be the specific pathways for AC; smoking might have a closer relationship with SCC.
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关键词
lung cancer,network annotation,pathway network,subtypes
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