Oncomicrobial Community Profiling Identifies Clinicomolecular and Prognostic Subtypes of Colorectal Cancer

Dmitri Mouradov ¹, Paul Greenfield ², Shan Li ³

¹Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
²Energy Business Unit, Commonwealth Scientific and Industrial Research Organization, Lindfield, New South Wales, Australia; School of Natural Sciences, Macquarie University, North Ryde, New South Wales, Australia.
³Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
⁴Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia; University of Melbourne Center for Cancer Research, Victorian Comprehensive Cancer Center, Melbourne, Victoria, Australia.
⁵Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia; University of Melbourne Center for Cancer Research, Victorian Comprehensive Cancer Center, Melbourne, Victoria, Australia; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁶Prince of Wales Clinical School and Lowy Cancer Research Center, UNSW Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁷School of Medical Sciences, UNSW Sydney, Sydney, New South Wales, Australia.
⁸Department of Surgery, Western Health, Footscray, Victoria, Australia.
⁹Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹⁰Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; Department of Medical Oncology, Western Health, St Albans, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia.
¹¹Molecular Diagnostics Solutions, Commonwealth Scientific and Industrial Research Organization Health and Biosecurity, Westmead, New South Wales, Australia.
¹²Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.

⁰Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.

Gastroenterology +

|

March 18, 2023

View abstract on PubMed

Summary

Gut microbiota dysbiosis is linked to colorectal cancer (CRC). This study identified three oncomicrobial community subtypes (OCSs) in CRC tissues, offering a new framework for CRC prognostication and targeted therapies.

Area Of Science

Microbiome research
Cancer genomics
Molecular pathology

Background

Gut microbiota dysbiosis is associated with colorectal cancer (CRC) development.
Microbiota-based stratification of CRC and its relation to clinicomolecular features and prognosis requires further clarification.

Purpose Of The Study

To stratify colorectal cancer (CRC) tissues based on microbiota composition.
To investigate the relationship between microbiota subtypes and clinicomolecular characteristics, including mutations and molecular subtypes.
To assess the prognostic implications of identified microbiota subtypes in CRC patients.

Main Methods

Bacterial 16S rRNA gene sequencing was performed on tumor and normal mucosa from 423 CRC patients (Stage I-IV).
Tumors were characterized for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), mutations (APC, BRAF, KRAS, PIK3CA, FBXW7, SMAD4, TP53), chromosome instability (CIN), mutation signatures, and consensus molecular subtypes (CMS).
Microbial clusters (OCSs) were validated in an independent cohort of 293 Stage II/III CRC tumors.

Main Results

Three distinct oncomicrobial community subtypes (OCSs) were identified: OCS1 (oral pathogens, proteolytic), OCS2 (Firmicutes/Bacteroidetes, saccharolytic), and OCS3 (Escherichia/Pseudescherichia/Shigella, fatty acid β-oxidation).
OCS1 was associated with right-sided, high-grade, MSI-high, CIMP-positive, CMS1, BRAF V600E, and FBXW7 mutations, and specific MSI-related mutation signatures.
OCS1 and OCS3 were linked to poorer overall survival in microsatellite-stable and left-sided tumors compared to OCS2, indicating prognostic significance.

Conclusions

Oncomicrobial community subtypes (OCSs) provide a robust stratification of colorectal cancer (CRC) with distinct clinicomolecular features and outcomes.
This microbiota-based classification offers a framework for refining CRC prognostication.
Findings support the development of microbiota-targeted interventions for CRC treatment.

Keywords:

Clinicomolecular Subtypes Colorectal Cancer Microbiota Classification Prognosis

Related Concept Videos

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...