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Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.

ABSTRACT: Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer?associated mortality in the world. However, its mechanisms of occurrence and development have not been clearly elucidated. Furthermore, there is no effective tumor marker for GC. Using DNA microarray analysis, the present study revealed genetic alterations, screened out core genes as novel markers and discovered pathways for potential therapeutic targets. Differentially expressed genes (DEGs) between GC and adjacent normal tissues were identified, followed by pathway enrichment analysis of DEGs. Next, the protein?protein interaction (PPI) network of DEGs was built and visualized. Analyses of modules in the PPI network were then performed to identify the functional core genes. Finally, survival analysis of core genes was conducted. A total of 256 genes were identified as DEGs between the GC samples and normal samples, including 169 downregulated and 87 upregulated genes. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the present study identified a total of 143 GO terms and 21 pathways. Six clusters of functional modules were identified, and the genes associated with these modules were screened out as the functional core genes. Certain core genes, including collagen type 12 ?1 chain (COL12A1), glutathione S?transferase ?3 (GSTA3), fibrinogen ? chain (FGA) and fibrinogen ? chain (FGG), were the first reported to be associated with GC. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3 (P=3.4x10?6), FGA (P=0.00075) and FGG (P=1.4x10?5), were significant poor prognostic factors and therefore, potential targets to improve diagnosis, optimize chemotherapy and predict prognostic outcomes.

SUBMITTER: Duan S

PROVIDER: S-EPMC6131538 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.

Duan Shijie S Gong Baocheng B Wang Pengliang P Huang Hanwei H Luo Lei L Liu Funan F

Molecular medicine reports 20180809 4

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer‑associated mortality in the world. However, its mechanisms of occurrence and development have not been clearly elucidated. Furthermore, there is no effective tumor marker for GC. Using DNA microarray analysis, the present study revealed genetic alterations, screened out core genes as novel markers and discovered pathways for potential therapeutic targets. Differentially expressed genes (DEGs) between GC ...[more]

PMID: 30106150

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Project description:Oral squamous cell carcinoma (OSCC) is a life?threatening disease with a poor prognosis. Although previous studies have reported that the methylation of certain genes is associated with the pathogenesis of OSCC, the methylation of genes that have relevance to OSCC progression is not clearly documented. The present study aimed to gain insights into the mechanisms underlying DNA methylation regulation associated with OSCC progression and to identify potential prognostic markers for OSCC treatment. DNA methylation dataset GSE41114 and gene expression dataset GSE74530 were downloaded from the Gene Expression Omnibus database. The global methylation status of OSCC tumor samples and normal control samples was determined, and differentially methylated genes (DMGs) in OSCC samples compared with control samples were identified. The mRNA expression data were then integrated to identify differentially expressed genes (DEGs) in OSCC samples compared with control samples. Overlapping genes between DEGs and DMGs were identified, and functional enrichment analysis was performed. In addition, survival analysis of the overlapping genes was performed to screen genes with prognostic significance in OSCC. A total of 40,115 differential methylation CpG sites spanning 3,360 DMGs were identified; CpG sites in the promoter, gene body and intergenic regions were generally highly hypermethylated or hypomethylated. Additionally, 508 DEGs in OSCC samples were identified, including 332 upregulated and 176 downregulated genes. A total of 82 overlapping genes between DEGs and DMGs were found, which were mainly involved in protein metabolism, regulation of the metabolic process and the immune system. Additionally, differential methylation or expression of several genes, including fibroblast activation protein ? (FAP), interferon ? inducible protein 27 (IFI27), laminin subunit ?2 (LAMC2), matrix metallopeptidase 1 (MMP1), serine peptidase inhibitor Kazal?type 5 (SPINK5) and zinc finger protein 662 (ZNF662), was significantly associated with the survival of OSCC patients, and their differential expression in OSCC patients was further confirmed by reverse transcription?quantitative polymerase chain reaction in OSCC and normal oral cell lines. Overall, FAP, IFI27, LAMC2, MMP1, SPINK5 and ZNF662 genes caused by epigenetic changes via DNA methylation may be associated with the development and progression of OSCC, and should be valuable OSCC therapeutic biomarkers.

Dataset Information

Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.

Publications

Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.

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