Distinct intratumoral microbiome of young-onset and average-onset colorectal cancerResearch in context
Shimoli V. Barot,
Naseer Sangwan,
Kanika G. Nair,
Stephanie L. Schmit,
Shao Xiang,
Suneel Kamath,
David Liska,
Alok A. Khorana
Affiliations
Shimoli V. Barot
Cleveland Clinic Taussig Cancer Institute, Department of Hematology-Oncology, USA
Naseer Sangwan
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
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
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
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Suneel Kamath
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
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
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; Corresponding author. Taussig Cancer Institute, 10201 Carnegie Avenue, CA-6, Cleveland, OH 44195, USA.
Summary: Background: The unexplained rise of young-onset CRC (yoCRC, age 60) has not been fully investigated. 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: 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 × 10−5) and varied beta diversity (R2 = 0.31, p = 0.013) than aoCRC tumors. yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella. Akkermansia had a predominantly negative correlation with the microbial communities in yoCRC tumors. yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, stage, and obesity. Fusobacterium (R2 = −0.23, p = 0.001) and Akkermansia (R2 = 0.05, p = 0.001) abundance correlated with overall survival in yoCRC. Interpretation: 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: Sondra and Stephen Hardis Chair in Oncology Research (A.A.K.)
