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Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis.

ABSTRACT: AIM:Cholangiocarcinoma (CCA) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common primary tumor of the liver. However, the pivotal roles of molecular biomarkers in oncogenesis of CCA are unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and treatment targets. METHOD:The data of mRNA sequencing and clinical information of CCA patients in The Cancer Genome Atlas was analyzed by weighted gene coexpression network analysis (WGCNA). Modules and clinical traits were constructed according to Pearson's correlation analysis, and Gene Ontology and pathway enrichment analysis were applied. Hub genes of these modules were screened by intramodule analysis; Cytoscape with Search Tool for the Retrieval of Interacting Genes was utilized to visualize protein-protein interaction of these modules; hub genes of these modules were validated afterwards. Furthermore, the significance of these genes was confirmed by survival analysis. RESULTS:Genes MRPS18A, CST1, and SCP2 were identified as candidate genes in the module, which was associated with clinical traits including pathological stage, histological grade, and liver function and which also affected overall survival of CCA patients. Nineteen hub genes were analyzed together and were associated with progression and prognosis of CCA. Survival analyses found that several of the multiple genes could serve as biomarkers to stratify CCA patients into low- and high-risk groups. CONCLUSION:These candidate genes could be involved in progression of CCA, which could serve as novel prognostic markers and treatment targets. Moreover, most of them were first reported in CCA and deserve further research.

SUBMITTER: Tian A

PROVIDER: S-EPMC6899837 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis.

Tian Aiping A Pu Ke K Li Boxuan B Li Min M Liu Xiaoguang X Gao Liping L Mao Xiaorong X

Hepatology research : the official journal of the Japan Society of Hepatology 20190716 10

<h4>Aim</h4>Cholangiocarcinoma (CCA) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common primary tumor of the liver. However, the pivotal roles of molecular biomarkers in oncogenesis of CCA are unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and treatment targets.<h4>Method</h4>The data of mRNA sequencing and clinical information of CCA patients in The Cancer Genome Atlas was ana ...[more]

PMID: 31177590

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Project description:Purpose:Despite advances in characterizing the neurobiology of emotional disorders, there is still a significant lack of scientific understanding of the pathophysiological mechanisms governing major depressive disorder (MDD). This study attempted to elucidate the molecular circuitry of MDD and to identify more potential genes associated with the pathogenesis of the disease. Patients and Methods:Microarray data from the GSE98793 dataset were downloaded from the NCBI Gene Expression Omnibus (GEO) database, including 128 patients with MDD and 64 healthy controls. Weighted gene coexpression network analysis (WGCNA) was performed to find modules of differentially expressed genes (DEGs) with high correlations followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to obtain further biological insight into the top three key modules. The protein-protein interaction (PPI) network, the modules from the PPI network, and the gene annotation enrichment of modules were analyzed, as well. Results:We filtered 3276 genes that were considered significant DEGs for further WGCNA analysis. By performing WGCNA, we found that the turquoise, blue and brown functional modules were all strongly correlated with MDD development, including immune response, neutrophil degranulation, ribosome biogenesis, T cell activation, glycosaminoglycan biosynthetic process, and protein serine/threonine kinase activator activity. Hub genes were identified in the key functional modules that might have a role in the progression of MDD. Functional annotation showed that these modules primarily enriched such KEGG pathways as the TNF signaling pathway, T cell receptor signaling pathway, primary immunodeficiency, Th1, Th2 and Th17 cell differentiation, autophagy and RNA degradation and oxidative phosphorylation. These results suggest that these genes are closely related to autophagy and cellular immune function. Conclusion:The results of this study may help to elucidate the pathophysiology of MDD development at the molecular level and explore the potential molecular mechanisms for new interventional strategies.

Dataset Information

Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis.

Publications

Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis.

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