Re-purposing 16S rRNA gene sequence data from within case paired tumor biopsy and tumor-adjacent biopsy or fecal samples to identify microbial markers for colorectal cancer

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study design
Shah MS, DeSantis T, Yamal JM, Weir T, Ryan EP, Cope JL, Hollister EB
PloS one
Microbes colonizing colorectal cancer (CRC) tumors have the potential to affect disease, and vice-versa. The manner in which they differ from microbes in physically adjacent tissue or stool within the case in terms of both, taxonomy and biological activity remains unclear. In this study, we systematically analyzed previously published 16S rRNA sequence data from CRC patients with matched tumor:tumor-adjacent biopsies (n = 294 pairs, n = 588 biospecimens) and matched tumor biopsy:fecal pairs (n = 42 pairs, n = 84 biospecimens). Procrustes analyses, random effects regression, random forest (RF) modeling, and inferred functional pathway analyses were conducted to assess community similarity and microbial diversity across heterogeneous patient groups and studies. Our results corroborate previously reported association of increased Fusobacterium with tumor biopsies. Parvimonas and Streptococcus abundances were also elevated while Faecalibacterium and Ruminococcaceae abundances decreased in tumors relative to tumor-adjacent biopsies and stool samples from the same case. With the exception of these limited taxa, the majority of findings from individual studies were not confirmed by other 16S rRNA gene-based datasets. RF models comparing tumor and tumor-adjacent specimens yielded an area under curve (AUC) of 64.3%, and models of tumor biopsies versus fecal specimens exhibited an AUC of 82.5%. Although some taxa were shared between fecal and tumor samples, their relative abundances varied substantially. Inferred functional analysis identified potential differences in branched amino acid and lipid metabolism. Microbial markers that reliably occur in tumor tissue can have implications for microbiome based and microbiome targeting therapeutics for CRC.

Experiment 1


Curated date: 2022/01/03

Curator: Itslanapark

Revision editor(s): WikiWorks753, Itslanapark


Location of subjects Country from which study subjects were recruited
China, Germany, Ireland, Malaysia, Netherlands, Spain, United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
colorectal cancer cancer of colorectum,cancer of large bowel,cancer of large intestine,cancer of the large bowel,colon cancer,colorectal cancer,colorectum cancer,CRC,large intestine cancer,malignant colorectal neoplasm,malignant colorectal tumor,malignant colorectum neoplasm,malignant large bowel neoplasm,malignant large bowel tumor,malignant large intestine neoplasm,malignant large intestine tumor,malignant neoplasm of colorectum,malignant neoplasm of large bowel,malignant neoplasm of large intestine,malignant neoplasm of the large bowel,malignant neoplasm of the large intestine,malignant tumor of large bowel,malignant tumor of large intestine,malignant tumor of the large bowel,malignant tumor of the large intestine
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
CRC patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients diagnosed with colorectal cancer

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina, Roche454