Dataset Information

Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA.

ABSTRACT: Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pathological stages including normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and early, advanced HCC and very advanced HCC. Among the eight consecutive pathological stages, five representative modules are selected to perform canonical pathway enrichment and upstream regulator analysis by using ingenuity pathway analysis (IPA) software. We found that cell cycle related biological processes were activated at four neoplastic stages, and the degree of activation of the cell cycle corresponded to the deterioration degree of HCC. The orange and yellow modules enriched in energy metabolism, especially oxidative metabolism, and the expression value of the genes decreased only at four neoplastic stages. The brown module, enriched in protein ubiquitination and ephrin receptor signaling pathways, correlated mainly with the very early stage of HCC. The darkred module, enriched in hepatic fibrosis/hepatic stellate cell activation, correlated with the cirrhotic stage only. The high degree hub genes were identified based on the protein-protein interaction (PPI) network and were verified by Kaplan-Meier survival analysis. The novel five high degree hub genes signature that was identified in our study may shed light on future prognostic and therapeutic approaches. Our study brings a new perspective to the understanding of the key pathways and genes in the dynamic changes of HCC progression. These findings shed light on further investigations.

SUBMITTER: Yin L

PROVIDER: S-EPMC5852588 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA.

Yin Li L Cai Zhihui Z Zhu Baoan B Xu Cunshuan C

Genes 20180214 2

Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pa ...[more]

PMID: 29443924

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Project description:Chronic kidney disease (CKD) is a highly heterogeneous nephrosis that occurs when the structure and function of the kidney is damaged. Gene expression studies have been widely used to elucidate various biological processes; however, the gene expression profile of CKD is currently unclear. The present study aimed to identify diagnostic biomarkers and therapeutic targets using renal biopsy sample data from patients with CKD. Gene expression data from 30 patients with CKD and 21 living donors were analyzed by weighted gene co‑expression network analysis (WGCNA), in order to identify gene networks and profiles for CKD, as well as its specific characteristics, and to potentially uncover diagnostic biomarkers and therapeutic targets for patients with CKD. In addition, functional enrichment analysis was performed on co‑expressed genes to determine modules of interest. Four co‑expression modules were constructed from the WGCNA. The number of genes in the constructed modules ranged from 269 genes in the Turquoise module to 60 genes in the Yellow module. All four co‑expression modules were correlated with CKD clinical traits (P<0.05). For example, the Turquoise module, which mostly contained genes that were upregulated in CKD, was positively correlated with CKD clinical traits, whereas the Blue, Brown and Yellow modules were negatively correlated with clinical traits. Functional enrichment analysis revealed that the Turquoise module was mainly enriched in genes associated with the 'defense response', 'mitotic cell cycle' and 'collagen catabolic process' Gene Ontology (GO) terms, implying that genes involved in cell cycle arrest and fibrogenesis were upregulated in CKD. Conversely, the Yellow module was mainly enriched in genes associated with 'glomerulus development' and 'kidney development' GO terms, indicating that genes associated with renal development and damage repair were downregulated in CKD. The hub genes in the modules were acetyl‑CoA carboxylase α, cyclin‑dependent kinase 1, Wilm's tumour 1, NPHS2 stomatin family member, podocin, JunB proto‑oncogene, AP‑1 transcription factor subunit, activating transcription factor 3, forkhead box O1 and v‑abl Abelson murine leukemia viral oncogene homolog 1, which were confirmed to be significantly differentially expressed in CKD biopsies. Combining the eight hub genes enabled a high capacity for discrimination between patients with CKD and healthy subjects, with an area under the receiver operating characteristic curve of 1.00. In conclusion, this study provided a framework for co‑expression modules of renal biopsy samples from patients with CKD and living donors, and identified several potential diagnostic biomarkers and therapeutic targets for CKD.

Dataset Information

Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA.

Publications

Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA.

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