Dataset Information

[Expression characteristics and functional analysis of ELK3 in gastric cancer].

ABSTRACT:

Objective

To explore the expression characteristics of ELK3 and its role in the occurrence, progression and prognosis of gastric cancer.

Methods

We analyzed the expression characteristics of ELK3 in gastric cancer based on E-MTAB-6693 dataset and explored the prognostic value of ELK3 using Kaplan-Meier survival analysis and univariate and multivariate Cox regression analysis. Chip-Atlas, ChipBase, Genes Transcription Regulation Database, and hTFtarget were used for predicting the target genes of ELK3 and constructing the transcription regulation network. Functional enrichment analysis of the target genes was performed using R software. The proportions of infiltrating immune cells in gastric cancer were analyzed using Cibersort tool, and the Pearson coefficients between ELK3 and these cells were calculated. The expression profile of ELK3 was verified based on Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases. We also collected 5 pairs of gastric cancer and adjacent tissue samples and detected the expression of ELK3 at both the mRNA and protein levels using RT-PCR and Western blotting.

Results

In public datasets and clinical samples, ELK3 was highly expressed in gastric cancer (P < 0.05), and its expression increased with the progression of M stage, AJCC stage, and perineural invasion (P < 0.05). ELK3 expression was correlated with N stage, AJCC stage, Lauren classification, differentiation, pathological classification, and microsatellite status of gastric cancer (P < 0.05). A high expression of ELK3 was associated with significantly reduced overall survival and disease-free survival of the patients, and served as an independent prognostic factor of gastric cancer (P < 0.05). Comprehensive analysis identified 176 potential target genes of ELK3, and enrichment analysis showed that ELK3 may regulate Rap1, AMPK, chemokines, VEGF, TNF, and tumor PD-L1/PD-1 signaling (PP < 0.05). The expression of ELK3 was negatively correlated with regulatory T cells, follicular helper T cells, and CD8+T cells in gastric cancer (P < 0.05).

Conclusion

ELK3 acts as an oncogene in gastric cancer, and its high expression may promote the occurrence, progression and immune escape of gastric cancer.

SUBMITTER: Zhou L

PROVIDER: S-EPMC8526318 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

[Expression characteristics and functional analysis of ELK3 in gastric cancer].

Zhou L L Wu Y Y Xin L L

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20210801 9

<h4>Objective</h4>To explore the expression characteristics of ELK3 and its role in the occurrence, progression and prognosis of gastric cancer.<h4>Methods</h4>We analyzed the expression characteristics of ELK3 in gastric cancer based on E-MTAB-6693 dataset and explored the prognostic value of ELK3 using Kaplan-Meier survival analysis and univariate and multivariate Cox regression analysis. Chip-Atlas, ChipBase, Genes Transcription Regulation Database, and hTFtarget were used for predicting the ...[more]

PMID: 34658341

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Project description:BackgroundNET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC.MethodsAn in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance.ResultsGC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells.ConclusionsNET1 plays an important role in GC cell migration and invasion, key aspects of GC progression. Furthermore, the gene expression profile further elucidates the molecular mechanisms underpinning NET1-mediated aggressive GC cell behaviour.

Dataset Information

[Expression characteristics and functional analysis of ELK3 in gastric cancer].

Objective

Methods

Results

Conclusion

Publications

[Expression characteristics and functional analysis of ELK3 in gastric cancer].

Similar Datasets

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