Journal article
The tumor microbiome reacts to hypoxia and can influence response to radiation treatment in colorectal cancer
Cancer research communications, Vol.4(7), pp.1690-1701
06/21/2024
DOI: 10.1158/2767-9764.CRC-23-0367
PMCID: PMC11234499
PMID: 38904265
Abstract
Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation's ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA-seq data from the Oncology Research Information Exchange Network (ORIEN) database of colorectal cancer (CRC) patients treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 CRC cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, where tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-trophic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia appears to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes.Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation's ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA-seq data from the Oncology Research Information Exchange Network (ORIEN) database of colorectal cancer (CRC) patients treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 CRC cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, where tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-trophic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia appears to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes.
Details
- Title: Subtitle
- The tumor microbiome reacts to hypoxia and can influence response to radiation treatment in colorectal cancer
- Creators
- Martin Benej - The Ohio State UniversityRebecca Hoyd - The Ohio State UniversityMcKenzie Kreamer - The Ohio State UniversityCaroline E Wheeler - The Ohio State UniversityDennis J Grencewicz - The Ohio State UniversityFouad Choueiry - The Ohio State UniversityCarlos H F ChanYousef Zakharia - University of IowaQin Ma - The Ohio State UniversityRebecca D Dodd - University of IowaCornelia M Ulrich - Huntsman Cancer InstituteSheetal Hardikar - Huntsman Cancer InstituteMichelle L ChurchmanAhmad A Tarhini - Moffitt Cancer CenterLary A Robinson - Moffitt Cancer CenterEric A Singer - The Ohio State University Wexner Medical CenterAlexandra P Ikeguchi - University of OklahomaMartin D McCarter - University of Colorado Anschutz Medical CampusGabriel Tinoco - The Ohio State UniversityMarium Husain - The Ohio State UniversityNing Jin - The Ohio State University Wexner Medical CenterAik Choon Tan - Huntsman Cancer InstituteAfaf E G Osman - University of UtahIslam Eljilany - Moffitt Cancer CenterGregory Riedlinger - Rutgers, The State University of New JerseyBryan P Schneider - Indiana University BloomingtonKatarina Benejova - The Ohio State UniversityMartin Kery - The Ohio State UniversityIoanna Papandreou - The Ohio State University Wexner Medical CenterJiangjiang Zhu - The Ohio State UniversityNicholas Denko - The Ohio State UniversityDaniel Spakowicz - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.4(7), pp.1690-1701
- DOI
- 10.1158/2767-9764.CRC-23-0367
- PMID
- 38904265
- PMCID
- PMC11234499
- ISSN
- 2767-9764
- eISSN
- 2767-9764
- Language
- English
- Electronic publication date
- 06/21/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Surgery; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984643655202771
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