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Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer

Rachel V Purcell, View ORCID ProfileMartina Visnovska, Patrick J Biggs, Sebastian Schmeier, Frank A Frizelle
doi: https://doi.org/10.1101/153809
Rachel V Purcell
1Department of Surgery, University of Otago, Christchurch, New Zealand.
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Martina Visnovska
2Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand.
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  • ORCID record for Martina Visnovska
Patrick J Biggs
3Hopkirk Institute, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
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Sebastian Schmeier
2Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand.
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Frank A Frizelle
1Department of Surgery, University of Otago, Christchurch, New Zealand.
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Abstract

Colorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding. 16S rRNA analysis showed enrichment of Fusobacteria and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria in CMS1. A more detailed analysis of bacterial taxa using non-human RNA-sequencing reads uncovered distinct bacterial communities associated with each molecular subtype. The most highly enriched species associated with CMS1 included Fusobacterium hwasookii and Porphyromonas gingivalis. CMS2 was enriched for Selenomas and Prevotella species, while CMS3 had few significant associations. Targeted quantitative PCR validated these findings and also showed an enrichment of Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis in CMS1. In this study, we have successfully associated individual bacterial species to CRC subtypes for the first time.

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Posted June 22, 2017.
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Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer
Rachel V Purcell, Martina Visnovska, Patrick J Biggs, Sebastian Schmeier, Frank A Frizelle
bioRxiv 153809; doi: https://doi.org/10.1101/153809
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Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer
Rachel V Purcell, Martina Visnovska, Patrick J Biggs, Sebastian Schmeier, Frank A Frizelle
bioRxiv 153809; doi: https://doi.org/10.1101/153809

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