Dataset Information

A prognostic prediction system for hepatocellular carcinoma based on gene co-expression network.

ABSTRACT: In the present study, gene expression data of hepatocellular carcinoma (HCC) were analyzed by using a multi-step Bioinformatics approach to establish a novel prognostic prediction system. Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The overlapping differentially expressed genes (DEGs) between these two datasets were identified using the limma package in R. Prognostic genes were further identified by Cox regression using the survival package. The significantly co-expressed gene pairs were selected using the R function cor to construct the co-expression network. Functional and module analyses were also performed. Next, a prognostic prediction system was established by Bayes discriminant analysis using the discriminant.bayes function in the e1071 package, which was further validated in another independent GEO dataset. A total of 177 overlapping DEGs were identified from TCGA and the GEO dataset (GSE36376). Furthermore, 161 prognostic genes were selected and the top six were stanniocalcin 2, carbonic anhydrase 12, cell division cycle (CDC) 20, deoxyribonuclease 1 like 3, glucosylceramidase ?3 and metallothionein 1G. A gene co-expression network involving 41 upregulated and 52 downregulated genes was constructed. SPC24, endothelial cell specific molecule 1, CDC20, CDCA3, cyclin (CCN) E1 and chromatin licensing and DNA replication factor 1 were significantly associated with cell division, mitotic cell cycle and positive regulation of cell proliferation. CCNB1, CCNE1, CCNB2 and stratifin were clearly associated with the p53 signaling pathway. A prognostic prediction system containing 55 signature genes was established and then validated in the GEO dataset GSE20140. In conclusion, the present study identified a number of prognostic genes and established a prediction system to assess the prognosis of HCC patients.

SUBMITTER: Guan L

PROVIDER: S-EPMC6489019 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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A prognostic prediction system for hepatocellular carcinoma based on gene co-expression network.

Guan Lianyue L Luo Qiang Q Liang Na N Liu Hongyu H

Experimental and therapeutic medicine 20190417 6

In the present study, gene expression data of hepatocellular carcinoma (HCC) were analyzed by using a multi-step Bioinformatics approach to establish a novel prognostic prediction system. Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The overlapping differentially expressed genes (DEGs) between these two datasets were identified using the <i>limma</i> package in R. Prognostic genes were further identified by Cox regressi ...[more]

PMID: 31086582

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Project description:BackgroundGastric carcinoma is a very diverse disease. The progression of gastric carcinoma is influenced by complicated gene networks. This study aims to investigate the actual and potential prognostic biomarkers related to survival in gastric carcinoma patients to further our understanding of tumor biology.MethodsA weighted gene co-expression network analysis was performed with a transcriptome dataset to identify networks and hub genes relevant to gastric carcinoma prognosis. Data was obtained from 300 primary gastric carcinomas (GSE62254). A validation dataset (GSE34942 and GSE15459) and TCGA dataset confirmed the results. Gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were performed to identify the clusters responsible for the biological processes and pathways of this disease.ResultsA brown transcriptional module enriched in the organizational process of the extracellular matrix was significantly correlated with overall survival (HR = 1.586, p = 0.005, 95% CI [1.149-2.189]) and disease-free survival (HR = 1.544, p = 0.008, 95% CI [1.119-2.131]). These observations were confirmed in the validation dataset (HR = 1.664, p = 0.006, 95% CI [1.155-2.398] in overall survival). Ten hub genes were identified and confirmed in the validation dataset from this brown module; five key biomarkers (COL8A1, FRMD6, TIMP2, CNRIP1 and GPR124 (ADGRA2)) were identified for further research in microsatellite instability (MSI) and epithelial-tomesenchymal transition (MSS/EMT) gastric carcinoma molecular subtypes. A high expression of these genes indicated a poor prognosis.ConclusionA transcriptional co-expression network-based approach was used to identify prognostic biomarkers in gastric carcinoma. This method may have potential for use in personalized therapies, however, large-scale randomized controlled clinical trials and replication experiments are needed before these key biomarkers can be applied clinically.

Dataset Information

A prognostic prediction system for hepatocellular carcinoma based on gene co-expression network.

Publications

A prognostic prediction system for hepatocellular carcinoma based on gene co-expression network.

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