Biology subjects

Purcell, R. V.

Publications and source records attributed to Purcell, R. V..

3 recordsLinked to original sources

bioRxiv2019

Molecular subtyping improves prognostication of Stage 2 colorectal cancer

Post-surgical staging is the mainstay of prognostic stratification for colorectal cancer (CRC). Here, we compare TNM staging to consensus molecular subtyping (CMS) and assess the value of subtyping in addition to stratification by TNM. Three hundred and eight treatment-naive colorectal tumours were accessed from our institutional tissue bank. CMS was carried out using tumour gene-expression data. Staging and CMS were analysed with respect to clinicopathologic variables and patient outcome. CMS alone was not associated with survival, while TNM stage significantly explained mortality. Addition of CMS to TNM-stratified tumours showed a prognostic effect in stage 2 tumours; CMS3 tumours had a significantly lower overall survival (P = 0.006). Stage 2 patients with a good prognosis showed immune activation and up-regulation of tumour suppressor genes. Although stratification using CMS does not outperform TNM staging as a prognostic indicator, gene-expression based subtyping shows promise for improved prognostication in stage 2 CRC.

cancer biology↗

bioRxiv2019

MinION Sequencing of colorectal cancer tumour microbiomes - a comparison with amplicon-based and RNA-Sequencing

Recent evidence suggests a role for the gut microbiome in the development and progression of colorectal cancer. In this study we compare MinION sequencing with meta-transcriptomics and amplicon-based sequencing for microbiome analysis of colorectal tumour tissue samples. DNA and RNA were extracted from 11 colorectal tumour samples. RNA-Sequencing, 16S rRNA amplicon sequencing and MinION genomic sequencing was carried out and resulting data used as input for taxonomic classification using Kraken2. Taxonomic concordance between the three platforms at different taxonomic levels was tested on a per sample basis. The average number of reads per sample using RNA-Sequencing was more than 129 times that generated using MinION sequencing. However, the average read length of MinION sequences was more than 13 times that of RNA or 16S rRNA amplicon sequencing. 16S sequencing was less informative beyond the genus level, and both RNA-Sequencing and MinION sequencing could detect more phyla and genera in the same samples, compared to 16S sequencing. Long-read sequences generated using MinION sequencing can compensate for low numbers of reads for bacterial classification. MinION sequencing can discriminate between bacterial strains and plasmids and shows potential as a tool for microbiome sequencing of colorectal cancers in a clinical setting.

microbiology↗

bioRxiv2017

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

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.

cancer biology↗