Dataset Information

Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.

ABSTRACT:

Background

Characterization of the features associated with circulating tumor cells (CTCs) is one of major interests for predicting clinical outcome of colorectal cancer (CRC) patients. However, the molecular features of CTCs remain largely unclear.

Methods

For identification of key genes and pathways, GSE31023, contained CTCs from six metastatic CRC patients and three controls, was retrieved for differentially expressed gene (DEG) analysis. Protein-protein interaction networks of DEGs were constructed. Hub genes from the network were prognostic analyzed, as well as the association with tumor-infiltrating immune cells.

Results

1353 DEGs were identified between the CTC and control groups, with 403 genes upregulated and 950 downregulated. 32 pathways were significantly enriched in KEGG, with ribosome pathway as top. The top 10 hub genes were included, including eukaryotic translation elongation factor 2 (EEF2), ribosomal protein S2 (RPS2), ribosomal protein S5 (RPS5), ribosomal protein L3 (RPL3), ribosomal protein S3 (RPS3), ribosomal protein S14 (RPS14), ribosomal protein SA (RPSA), eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), ribosomal protein S15a (RPS15A), and ribosomal protein L4 (RPL4). The correlation between CD4⁺ T cells and RPS14 (correlation = -0.5) was the highest in colon cancer while CD8⁺ T and RPS2 (correlation = -0.53) was the highest in rectal cancer.

Conclusion

This study identified potential role of ribosome pathway in CTC, providing further insightful therapeutic targets and biomarkers for CRC.

SUBMITTER: Pan R

PROVIDER: S-EPMC8813301 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.

Pan Ruijun R Yu Chaoran C Shao Yanfei Y Hong Hiju H Sun Jing J Zhang Zhou Z Li Peiyong P Zheng Minhua M

Analytical cellular pathology (Amsterdam) 20220127

<h4>Background</h4>Characterization of the features associated with circulating tumor cells (CTCs) is one of major interests for predicting clinical outcome of colorectal cancer (CRC) patients. However, the molecular features of CTCs remain largely unclear.<h4>Methods</h4>For identification of key genes and pathways, GSE31023, contained CTCs from six metastatic CRC patients and three controls, was retrieved for differentially expressed gene (DEG) analysis. Protein-protein interaction networks of ...[more]

PMID: 35127345

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Project description:BackgroundThe anti-epidermal growth factor receptor (EGFR) antibody introduces adaptable variations to the transcriptome and triggers tumor immune infiltration, resulting in colorectal cancer (CRC) treatment resistance. We intended to identify genes that play essential roles in cetuximab resistance and tumor immune cell infiltration.MethodsA cetuximab-resistant CACO2 cellular model was established, and its transcriptome variations were detected by microarray. Meanwhile, public data from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database were downloaded. Integrated bioinformatics analysis was applied to detect differentially expressed genes (DEGs) between the cetuximab-resistant and the cetuximab-sensitive groups. Then, we investigated correlations between DEGs and immune cell infiltration. The DEGs from bioinformatics analysis were further validated in vitro and in clinical samples.ResultsWe identified 732 upregulated and 1259 downregulated DEGs in the induced cellular model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, along with Gene Set Enrichment Analysis and Gene Set Variation Analysis, indicated the functions of the DEGs. Together with GSE59857 and GSE5841, 12 common DEGs (SATB-2, AKR1B10, ADH1A, ADH1C, MYB, ATP10B, CDX-2, FAR2, EPHB2, SLC26A3, ORP-1, VAV3) were identified and their predictive values of cetuximab treatment were validated in GSE56386. In online Genomics of Drug Sensitivity in Cancer (GDSC) database, nine of twelve DEGs were recognized in the protein-protein (PPI) network. Based on the transcriptome profiles of CRC samples in TCGA and using Tumor Immune Estimation Resource Version 2.0, we bioinformatically determined that SATB-2, ORP-1, MYB, and CDX-2 expressions were associated with intensive infiltration of B cell, CD4+ T cell, CD8+ T cell and macrophage, which was then validated the correlation in clinical samples by immunohistochemistry. We found that SATB-2, ORP-1, MYB, and CDX-2 were downregulated in vitro with cetuximab treatment. Clinically, patients with advanced CRC and high ORP-1 expression exhibited a longer progression-free survival time when they were treated with anti-EGFR therapy than those with low ORP-1 expression.ConclusionsSATB-2, ORP-1, MYB, and CDX-2 were related to cetuximab sensitivity as well as enhanced tumor immune cell infiltration in patients with CRC.

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Dataset Information

Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.

Background

Methods

Results

Conclusion

Publications

Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.

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