Distinct intratumoral microbiome of young-onset and average-onset colorectal cancer.

16S Colorectal cancer Dysbiosis Early-onset Microbiome Young-onset

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
01 Feb 2024
Historique:
received: 06 04 2023
revised: 09 01 2024
accepted: 11 01 2024
medline: 3 2 2024
pubmed: 3 2 2024
entrez: 2 2 2024
Statut: aheadofprint

Résumé

The unexplained rise of young-onset CRC (yoCRC, age <50 years) is of concern. Evidence suggests that microbial dysbiosis may be a contributing factor, but the tumor microbial profile of yoCRC in comparison to average-onset CRC (aoCRC, age >60) has not been fully investigated. 16S rRNA amplicon sequencing was performed in tumor and paired adjacent non-malignant fresh frozen tissue specimens prospectively collected from 136 yoCRC and 140 aoCRC patients. Phyloseq, microbiomeSeq, metagenomeSeq, and NetComi were utilized for bioinformatics analysis. Statistical tests included Fisher's exact test, ANOVA, PERMANOVA with Bonferroni correction, linear regression, and Wilcoxon test. p-value <0.05 was considered statistically significant. yoCRC patients were more likely to have left-sided (72.8 vs. 54.3%), rectal (36.7% vs. 25%), and stage IV (28% vs. 15%) tumors. yoCRC tumors had significantly higher microbial alpha diversity (p = 1.5 × 10 Our study provides a comprehensive understanding of the microbial perturbations in yoCRC tumors. We identify microbial candidates that may highlight a distinct pathogenesis of yoCRC and serve as preventive, diagnostic, and therapeutic targets. Sondra and Stephen Hardis Chair in Oncology Research (A.A.K.).

Sections du résumé

BACKGROUND BACKGROUND
The unexplained rise of young-onset CRC (yoCRC, age <50 years) is of concern. Evidence suggests that microbial dysbiosis may be a contributing factor, but the tumor microbial profile of yoCRC in comparison to average-onset CRC (aoCRC, age >60) has not been fully investigated.
METHODS METHODS
16S rRNA amplicon sequencing was performed in tumor and paired adjacent non-malignant fresh frozen tissue specimens prospectively collected from 136 yoCRC and 140 aoCRC patients. Phyloseq, microbiomeSeq, metagenomeSeq, and NetComi were utilized for bioinformatics analysis. Statistical tests included Fisher's exact test, ANOVA, PERMANOVA with Bonferroni correction, linear regression, and Wilcoxon test. p-value <0.05 was considered statistically significant.
FINDINGS RESULTS
yoCRC patients were more likely to have left-sided (72.8 vs. 54.3%), rectal (36.7% vs. 25%), and stage IV (28% vs. 15%) tumors. yoCRC tumors had significantly higher microbial alpha diversity (p = 1.5 × 10
INTERPRETATION CONCLUSIONS
Our study provides a comprehensive understanding of the microbial perturbations in yoCRC tumors. We identify microbial candidates that may highlight a distinct pathogenesis of yoCRC and serve as preventive, diagnostic, and therapeutic targets.
FUNDING BACKGROUND
Sondra and Stephen Hardis Chair in Oncology Research (A.A.K.).

Identifiants

DOI: 10.1016/j.ebiom.2024.104980 PMID: 38306898
pubmed: 38306898
pii: S2352-3964(24)00015-X
doi: 10.1016/j.ebiom.2024.104980
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104980

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests S.V.B., N.S., K.G.N., S.L.S., and S.X. report no conflicts of interest. S.K. reports consulting and advisory roles in Exelixis, Tempus, Guardant Health, and SeaGen. D.L. reports consulting and advisory roles in Olympus Medical Systems and research funding from Merck. A.A.K. reports consulting honoraria from Janssen, Bayer, BMS, Sanofi, Pfizer, and Anthos.

Auteurs

Shimoli V Barot (SV)

Cleveland Clinic Taussig Cancer Institute, Department of Hematology-Oncology, USA.

Naseer Sangwan (N)

Shared Laboratory Resources (SLR), Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Kanika G Nair (KG)

Cleveland Clinic Taussig Cancer Institute, Department of Hematology-Oncology, USA; Case Comprehensive Cancer Center, Cleveland, OH, USA; Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, OH, USA.

Stephanie L Schmit (SL)

Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, OH, USA; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA.

Shao Xiang (S)

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Suneel Kamath (S)

Cleveland Clinic Taussig Cancer Institute, Department of Hematology-Oncology, USA; Case Comprehensive Cancer Center, Cleveland, OH, USA; Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, OH, USA.

David Liska (D)

Case Comprehensive Cancer Center, Cleveland, OH, USA; Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, OH, USA; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.

Alok A Khorana (AA)

Cleveland Clinic Taussig Cancer Institute, Department of Hematology-Oncology, USA; Case Comprehensive Cancer Center, Cleveland, OH, USA; Center for Young-Onset Colorectal Cancer, Cleveland Clinic, Cleveland, OH, USA. Electronic address: khorana@ccf.org.

Classifications MeSH