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pmid:39027882

Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer.

Xiaoxia Tong · Li Ma · Di Wu · Yibing Liu · Yonglei Liu

Open medicine (Warsaw, Poland) · 2024 doi:10.1515/med-2024-0997

Paper

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Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer.
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10.1515/med-2024-0997
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Xiaoxia Tong
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Li Ma
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Di Wu
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Yibing Liu
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Yonglei Liu
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Open medicine (Warsaw, Poland)
year
2024
abstract
Backgrounds: The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex's role in gastric cancer (GC) is poorly understood. Methods: The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein-protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC. Results: The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5'-3' RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects. Conclusions: Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.
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To explore the potential prognostic values of INT subunits, we analyzed the relationship between INT subunit expressions and overall survival (OS) based on by K–M plotter website (http://kmplot.com/analysis/).
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Data availability statement: Publicly available datasets were analyzed in this study. This data can be found in online repositories: TCGA (https://www.cancer.gov/ccg/research/genome-sequencing/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE183904.
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n GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inh
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Although several subunits of INT complex have been implicated in multiple cancers, the complex's role in gastric cancer (GC) is poorly understood.\nMethods: The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein-protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC.\nResults: The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5'-3' RNA polymerase activity. 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