Journal article
Epigenetic Modulation, Intra-tumoral Microbiome and Immunity in Early Onset Colorectal Cancer
Cancer research communications, Vol.5(11), pp.1985-1997
11/2025
DOI: 10.1158/2767-9764.CRC-25-0177
PMCID: PMC12606411
PMID: 41134679
Abstract
The incidence of colorectal cancer (CRC) in young adults (age of diagnosis < 50 years old) has been rapidly increasing. Although ~20% of early-onset (EO) CRC cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. Non-genetic factors such as environmental exposure and lifestyle changes are likely to have a direct link to the increased incidence of sporadic EOCRC. We hypothesize that such factors may be observable as alterations in the epigenome, microbiome and immunome. We characterized DNA methylation signature and measured DNA methylation (DNAm) age in EOCRC by using The Cancer Genome Atlas (TCGA). Further, we carefully identified intra-tumoral microbes from TCGA and the Oncology Research Information Exchange Network (ORIEN) datasets and then related the microbes with deconvolved immune cell abundances in EOCRC. We observed DNAm age in EOCRC cohort were 12 years older when compared with average-onset CRC (AOCRC) cohort, by using three different epigenetic clocks. Differential methylated sites associated with gene expressions include CREB signaling in neurons, G protein coupled receptor signaling, phagosome formation and S100 family signaling. These differences were validated in the gene expression from TCGA and ORIEN. When compared the intra-tumoral microbes between EOCRC and AOCRC, no consistent differences were observed. Interestingly, the most abundant microbes interacted with the immune systems differently between the EOCRC and AOCRC tumors, characterized by more, larger, positive correlations in EOCRC. These data suggest epigenetic modulation and accelerated aging may play a key role in the development of EOCRC.
Details
- Title: Subtitle
- Epigenetic Modulation, Intra-tumoral Microbiome and Immunity in Early Onset Colorectal Cancer
- Creators
- Ning Jin - The Ohio State University Wexner Medical CenterRebecca Hoyd - The Ohio State UniversityAyse S Yilmaz - The Ohio State UniversityJiangjiang Zhu - The Ohio State UniversityYunzhou Liu - The Ohio State UniversityMalvenderjit S Jagjit Singh - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteDennis J Grencewicz - The Ohio State UniversityXiaokui Mo - The Ohio State UniversityMatthew F Kalady - The Ohio State University Wexner Medical CenterDaniel W Rosenberg - UConn HealthCaroline E Dravillas - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteEric A Singer - The Ohio State University Wexner Medical CenterJohn D Carpten - University of Southern CaliforniaCarlos H F Chan - University of IowaMichelle L Churchman - Aster Insights, Hudson, FL, United StatesNicholas Denko - The Ohio State UniversityFrances Di Clemente - Rutgers, The State University of New JerseyRebecca D Dodd - University of IowaIslam Eljilany - Moffitt Cancer CenterNaomi Fei - University of Iowa Hospitals and ClinicsSheetal Hardikar - Huntsman Cancer InstituteAlexandra P Ikeguchi - The University of Texas MD Anderson Cancer CenterAnjun Ma - The Ohio State UniversityQin Ma - The Ohio State UniversityMartin D McCarter - University of Colorado Anschutz Medical CampusAfaf E G Osman - University of UtahGregory Riedlinger - Rutgers, The State University of New JerseyLary A Robinson - Moffitt Cancer CenterBryan P Schneider - Indiana University BloomingtonAhmad A Tarhini - Moffitt Cancer CenterGabriel Tinoco - The Ohio State UniversityJane C Figueiredo - Cedars-Sinai Medical CenterYousef Zakharia - University of Iowa Hospitals and ClinicsCornelia M Ulrich - Huntsman Cancer InstituteAikChoon Tan - Huntsman Cancer InstituteDaniel Spakowicz - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.5(11), pp.1985-1997
- DOI
- 10.1158/2767-9764.CRC-25-0177
- PMID
- 41134679
- PMCID
- PMC12606411
- NLM abbreviation
- Cancer Res Commun
- ISSN
- 2767-9764
- eISSN
- 2767-9764
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- National Cancer Institute (NCI): K12CA133250 National Institute on Aging (NIA): K01AG070310 National Institutes of Health (NIH): P30CA042014, U01 CA206110 National Center for Advancing Translational Sciences (NCATS): 8UL1TR000090-05 Ohio State University (OSU)Alpha Omega Alpha Honor Medical Society (AOA)American Cancer Society (ACS)
This project was partly supported by the Paul Calabresi Career Development Award for Clinical Oncology (K12 Research Training K12CA133250; N. Jin); the Ohio State University Comprehensive Cancer Center and the NIH (P30CA016058); the Ohio State University Center for Clinical and Translational Science and the National Center for Advancing Translational Sciences (8UL1TR000090-05); the Huntsman Cancer Institute, Comprehensive Cancer Center at the University of Utah, and the NIH [P30CA042014 & U01 CA206110 (Ulrich, Hardikar, Figueiredo)]; an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship (D.J. Grencewicz); a Samuel J. Roessler Memorial Scholarship (D.J. Grencewicz); the National Institute on Aging (K01AG070310 to D. Spakowicz); and the American Cancer Society (to D. Spakowicz). This work was also supported by the Pelotonia Institute of Immuno-Oncology. The authors acknowledge the support and resources of the Ohio Supercomputing Center (PAS1695 and PCON0005). The results published here are in whole or in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. We would like to thank Angela Dahlberg, Editor, Division of Medical Oncology at the Ohio State University Comprehensive Cancer Center, for editing and proofreading the manuscript.
- Language
- English
- Electronic publication date
- 10/24/2025
- Date published
- 11/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Surgery; Radiation Oncology; Internal Medicine
- Record Identifier
- 9985016423502771
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