ArticleCancer management and research2021
Comprehensive Analysis to Identify Enhancer-Regulated Inflammation-Associated Genes in Lung Adenocarcinoma.
Article in Cancer management and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Elevated serum Slit3 independently predicts disease activity and interstitial lung disease in rheumatoid arthritis.Clinics (Sao Paulo, Brazil) · 2026Article
- Article
- Identification of a ZC3H12D-regulated competing endogenous RNA network for prognosis of lung adenocarcinoma at single-cell level.BMC cancer · 2022Article
- HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma.Frontiers in oncology · 2022Article
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3 authors.
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Abstract
objectiveThe purpose of this study was to identify prognostic inflammatory markers regulated by enhancers in lung adenocarcinoma (LUAD).
methodsInflammatory indices of 490 LUAD patients in TCGA database were calculated using genomic variation analysis (GSVA). Patients were divided into high- and low-inflammatory index groups. Fraction of 22 infiltrating immune cells was estimated using the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Gene set enrichment analysis (GSEA) was used to analyze gene enrichment. Differentially expressed genes were screened based on TCGA database. The H3K27ac ChIP-seq of A549 cells in GEO database (GSE42374) was analyzed to identify super enhancers. Kaplan-Meier method and multivariate Cox proportional hazards models were used for survival analysis. CCK8 and RT-qPCR were used for cellular level verification.
resultsInflammation was associated with better outcome in LUAD patients. Anti-cancer immune cell fractions were upregulated in high-inflammatory index group. Genes enriched in inflammation-related signaling pathways were positively correlated with high-inflammatory index group. A total of 146 upregulated genes regulated by enhancers were screened, of which five genes including GDF10, HPGDS, ABCA8, SLIT3 and ADAMTS8 had significant influence on prognosis. ChIP-seq analysis showed that TGFβ+TNFα treatment promoted the enhancer activation of the five genes. Cellular experiments revealed that there was no significant effect of TGFβ treatment on the five genes expression. TNFα treatment upregulated the five genes expression, while the BET-bromodomain inhibitor JQ1 restored the effect of TNFα. Overexpression of the five genes significantly inhibited the proliferation of A549 and H1299 cells.
conclusionGDF10, HPGDS, ABCA8, SLIT3 and ADAMTS8 were identified as enhancer-regulated prognostic inflammation-related biomarkers, and the expression of these genes inhibited proliferation of LUAD cells.
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