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Updated: Aug 9, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
The pan-cancer landscape of abnormal DNA methylation and intratumor microorganisms
Ping Zhou1, Simon L Lu2, Liang Chang1
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
Abstract:
Microorganisms play very important roles in carcinogenesis, tumor progression, and resistance upon treatment. Due to the challenge of accurately acquiring samples and quantifying low-biomass tissue microorganisms, most studies have focused on the effect of gut microorganisms on cancer treatments, especially the efficacy of immunotherapy. Although recent publications reveal the potential interactions between intratumor microorganisms and the immune microenvironment, whether and to what extent the intratumor microorganism could affect progression and treatment outcome remain controversial. This study is aiming to evaluate the associations among intratumor microorganisms, DNA methylation cancer driver genes, immune response, and clinical outcomes from a pan-cancer perspective, using 6,876 TCGA samples across 21 cancer types. We revealed that tumor microorganism dysbiosis is closely associated with the abnormal tumor methylome and/or tumor microenvironment, which might serve to enhance the proliferation ability and fitness for the therapy of tumors. These findings shed the light on a better understanding of the interactions between tumor cells and carcinogens during and after tumor formation, as well as microorganism-associated methylation alterations that could further serve as biomarkers for clinical outcome assessment.
Insights
Tumor microorganisms impact cancer progression and treatment. This study links microbial imbalance to altered tumor DNA methylation and immune microenvironments, suggesting potential biomarkers for clinical outcomes.
Area of Science:
- Oncology
- Microbiology
- Genomics
Background:
- Microorganisms influence cancer development, progression, and treatment resistance.
- Research often focuses on gut microbes, but intratumor microbes' roles are debated.
- Understanding intratumor microbes is crucial for cancer therapy and prognosis.
Purpose of the Study:
- To investigate associations between intratumor microorganisms, DNA methylation, immune response, and clinical outcomes.
- To analyze these interactions across 21 cancer types using The Cancer Genome Atlas (TCGA) data.
- To explore the potential of these interactions as biomarkers for cancer prognosis.
Main Methods:
- Utilized TCGA data from 6,876 cancer samples across 21 types.
- Analyzed intratumor microorganisms, DNA methylation patterns, and immune microenvironment data.
- Correlated microbial dysbiosis with genomic alterations and clinical outcomes.
Main Results:
- Tumor microorganism dysbiosis is linked to abnormal tumor methylomes and tumor microenvironments.
- These alterations may enhance tumor proliferation and treatment adaptability.
- Identified potential microorganism-associated methylation alterations impacting clinical outcomes.
Conclusions:
- Intratumor microorganisms significantly interact with the tumor methylome and immune microenvironment.
- Microbial dysbiosis influences cancer progression and therapeutic response.
- Microorganism-associated methylation changes may serve as novel biomarkers for assessing clinical outcomes.
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