Dataset Information

Identification of hub driving genes and regulators of lung adenocarcinoma based on the gene Co-expression network.

ABSTRACT: Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related deaths worldwide. Increasing evidence suggests that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can regulate target gene expression and participate in tumor genesis and progression. However, hub driving genes and regulators playing a potential role in LUAD progression have not been fully elucidated yet. Based on data from The Cancer Genome Atlas database, 2837 differentially expressed genes, 741 DE-regulators were screened by comparing cancer tissues with paracancerous tissues. Then, 651 hub driving genes were selected by the topological relation of the protein-protein interaction network. Also, the target genes of DE-regulators were identified. Moreover, a key gene set containing 65 genes was obtained from the hub driving genes and target genes intersection. Subsequently, 183 hub regulators were selected based on the analysis of node degree in the ceRNA network. Next, a comprehensive analysis of the subgroups and Wnt, mTOR, and MAPK signaling pathways was conducted to understand enrichment of the subgroups. Survival analysis and a receiver operating characteristic curve analysis were further used to screen for the key genes and regulators. Furthermore, we verified key molecules based on external database, LRRK2, PECAM1, EPAS1, LDB2, and HOXA11-AS showed good results. LRRK2 was further identified as promising biomarker associated with CNV alteration and various immune cells' infiltration levels in LUAD. Overall, the present study provided a novel perspective and insight into hub driving genes and regulators in LUAD, suggesting that the identified signature could serve as an independent prognostic biomarker.

SUBMITTER: Xu Z

PROVIDER: S-EPMC7108999 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Identification of hub driving genes and regulators of lung adenocarcinoma based on the gene Co-expression network.

Xu Zihao Z Wu Zilong Z Xu Jiatang J Zhang Jingtao J Yu Bentong B

Bioscience reports 20200401 4

Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related deaths worldwide. Increasing evidence suggests that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can regulate target gene expression and participate in tumor genesis and progression. However, hub driving genes and regulators playing a potential role in LUAD progression have not been fully elucidated yet. Based on data from The Cancer Genome Atlas database, 2837 differentially expressed genes, 741 DE-regulators ...[more]

PMID: 32196072

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Project description:The aim of the present study was to identify hub genes and signaling pathways associated with bladder cancer (BC) utilizing centrality analysis and pathway enrichment analysis. The differentially expressed genes (DEGs) were screened from the ArrayExpress database between normal subjects and BC patients. Co-expression networks of BC were constructed using differentially co-expressed genes and links, and hub genes were investigated by degree centrality analysis of co-expression networks in BC. The enriched signaling pathways were investigated by Kyoto Encyclopedia of Genes and Genomes database analysis based on the DEGs. The hub gene expression in BC tissues was validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. A total of 329 DEGs were screened, including 147 upregulated and 182 downregulated genes. The co-expression network constructed between BC and normal controls consisted of 182 nodes and 434 edges, and the two genes in each gene pair were differentially co-expressed genes. Centrality analysis of co-expression networks suggested that the top 5 hub genes with high degree included lectin, galactoside-binding, soluble, 4 (LGALS4), protein tyrosine phosphatase, receptor type N2 (PTPRN2), transmembrane protease, serine 11E (TMPRSS11E), tripartite motif containing 31 (TRIM31) and potassium voltage-gated channel subfamily D member 3 (KCND3). Pathway analysis revealed that the 329 DEGs were significantly enriched in 5 terms (cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway and peroxisome proliferator-activated receptor signaling pathway). According to RT-qPCR and western blot analysis, 4/5 hub genes were significantly expressed, including LGALS4, PTPRN2, TMPRSS11E, TRIM31; however, KCND3 was not significantly expressed. In the present study, 5 hub genes were successfully identified (LGALS4, PTPRN2, TMPRSS11E, TRIM31 and KCND3) and 5 biological pathways that may be underlying biomarkers for early diagnosis and treatment associated with bladder cancer were revealed.

Project description:ObjectiveTo investigate the differential expression gene modules and hub genes associated with Alzheimer's disease (AD) by weighted gene co-expression network analysis (WGCNA) and annotate the biological functions of these modules.MethodsWe downloaded transcriptome sequencing data from the GEO database, and according to the correlation of the genes, a gene co-expression network was constructed with the parameter setting of β=8 and a correlation coefficient threshold of 0.85. Pearson correlation test was used to calculate the correlation between the module genes and clinical traits to screen the gene modules significantly associated with AD and identify the hub genes according to the connectivity within modules. GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the modules. A cell model of AD was established in SH-SY5Y cells by Aβ1-42 treatment, and the mRNA expression levels of the hub genes were compared between the Aβ1-42-treated cells and the control cells.ResultsTen gene co-expression modules were constructed based on the correlations of gene expression, in which the brown (r=0.66, P < 0.001) and turquoise modules (r=-0.68, P < 0.001) were significantly correlated with the AD group. Forty-eight genes were identified as the hub genes in the co-expression network. Function annotation revealed that the genes in both modules were mainly enriched in DNA damage and repair pathways and metabolism-related pathways. Differential expression analysis of the genes revealed that the genes DNASE1, TEKT2 and MTSS1L were highly expressed while ACP2, LANCL2 and GMPR2 were lowly expressed in AD group. The results of cell experiment confirmed the up-regulation of DNASE1, TEKT2 and MTSS1L genes and the down-regulation of ACP2, LANCL2, and GMPR2 in Aβ1-42-treated SH-SY5Y cells (P < 0.01).ConclusionThe brown and turquoise modules are closely correlated with AD. The hub genes including MTSS1L, GMPR2, ACP2, ACTG1 and LANCL2 selected from the modules may participate in AD pathogenesis by regulating DNA damage and repair.

Dataset Information

Identification of hub driving genes and regulators of lung adenocarcinoma based on the gene Co-expression network.

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Identification of hub driving genes and regulators of lung adenocarcinoma based on the gene Co-expression network.

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