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Updated: Jun 14, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the
Beatriz Andrea Otálora-Otálora1, César Payán-Gómez2, Juan Javier López-Rivera3
1Grupo de Investigación INPAC, Unidad de Investigación, Fundación Universitaria Sanitas, Bogotá, Colombia.
Background:
The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer.
Methods:
Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis.
Results:
The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network.
Conclusion:
The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.
Insights
This study reveals a common regulatory network of transcription factors in lung, gastric, and colon cancers. This network influences cell plasticity and interacts with the microbiome, impacting cancer progression and mortality.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Lung, colon, and gastric cancers remain leading causes of cancer mortality globally.
- Current diagnostic and treatment strategies based on histology and biomarkers have limited impact on mortality rates.
Purpose of the Study:
- To identify a common regulatory network of transcription factors across lung, gastric, and colon cancers.
- To investigate the role of this network in cell phenotypic plasticity and cancer hallmarks.
- To explore the potential crosstalk with the microbiome network in the oral-gut-lung axis.
Main Methods:
- Transcriptomic analysis of 25 datasets (10 lung, 10 gastric, 5 colon cancer).
- Bioinformatic pipeline utilizing R language libraries and DAVID gene enrichment analyses.
- Identification of a common regulatory metafirm network of transcription factors and target genes.
Main Results:
- A common transcriptomic network involving transcription factors (SOX4, TCF3, TEAD4, ETV4, FOXM1) was identified.
- These factors are linked to stem cell programming and cancer progression.
- The network facilitates interactions with microorganisms (e.g., HTLV-1, HPV, EBV, SARS-CoV-2) and activates signaling pathways (MAPK, WNT, IFN).
Conclusions:
- Global transcriptomic network analysis highlights key transcription factor interactions in lung, colon, and gastric cancers.
- These interactions regulate cancer-cell membrane receptor expression for microbiome interaction during tumorigenesis.
- The findings suggest a novel therapeutic target for common cancers.
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