Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue

ABSTRACT As research focusing on the colorectal cancer fecal microbiome using shotgun sequencing continues, increasing evidence has supported correlations between colorectal carcinomas (CRCs) and fecal microbiome dysbiosis. However, large-scale on-site and off-site (surrounding adjacent) tissue micr...

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Autores principales: Zongchao Mo, Peide Huang, Chao Yang, Sihao Xiao, Guojia Zhang, Fei Ling, Lin Li
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:319547ada5104d97b8e7ab82ab8369bb2021-12-02T18:15:47ZMeta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue10.1128/mSystems.00138-202379-5077https://doaj.org/article/319547ada5104d97b8e7ab82ab8369bb2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00138-20https://doaj.org/toc/2379-5077ABSTRACT As research focusing on the colorectal cancer fecal microbiome using shotgun sequencing continues, increasing evidence has supported correlations between colorectal carcinomas (CRCs) and fecal microbiome dysbiosis. However, large-scale on-site and off-site (surrounding adjacent) tissue microbiome characterization of CRC was underrepresented. Here, considering each taxon as a feature, we demonstrate a machine learning-based method to investigate tissue microbial differences among CRC, colorectal adenoma (CRA), and healthy control groups using 16S rRNA data sets retrieved from 15 studies. A total of 2,099 samples were included and analyzed in case-control comparisons. Multiple methods, including differential abundance analysis, random forest classification, cooccurrence network analysis, and Dirichlet multinomial mixture analysis, were conducted to investigate the microbial signatures. We showed that the dysbiosis of the off-site tissue of colonic cancer was distinctive and predictive. The AUCs (areas under the curve) were 80.7%, 96.0%, and 95.8% for CRC versus healthy control random forest models using stool, tissue, and adjacent tissue samples and 69.9%, 91.5%, and 89.5% for the corresponding CRA models, respectively. We also found that the microbiota ecologies of the surrounding adjacent tissues of CRC and CRA were similar to their on-site counterparts according to network analysis. Furthermore, based on the enterotyping of tissue samples, the cohort-specific microbial signature might be the crux in addressing classification generalization problems. Despite cohort heterogeneity, the dysbiosis of lesion-adjacent tissues might provide us with further perspectives in demonstrating the role of the microbiota in colorectal cancer tumorigenesis. IMPORTANCE Turbulent fecal and tissue microbiome dysbiosis of colorectal carcinoma and adenoma has been identified, and some taxa have been proven to be carcinogenic. However, the microbiomes of surrounding adjacent tissues of colonic cancerous tissues were seldom investigated uniformly on a large scale. Here, we characterize the microbiome signatures and dysbiosis of various colonic cancer sample groups. We found a high correlation between colorectal carcinoma adjacent tissue microbiomes and their on-site counterparts. We also discovered that the microbiome dysbiosis in adjacent tissues could discriminate colorectal carcinomas from healthy controls effectively. These results extend our knowledge on the microbial profile of colorectal cancer tissues and highlight microbiota dysbiosis in the surrounding tissues. They also suggest that microbial feature variations of cancerous lesion-adjacent tissues might help to reveal the microbial etiology of colonic cancer and could ultimately be applied for diagnostic and screening purposes.Zongchao MoPeide HuangChao YangSihao XiaoGuojia ZhangFei LingLin LiAmerican Society for Microbiologyarticle16S rRNAcolorectal canceradenomacarcinomaadjacent tissuesnetworkMicrobiologyQR1-502ENmSystems, Vol 5, Iss 2 (2020)
institution DOAJ
collection DOAJ
language EN
topic 16S rRNA
colorectal cancer
adenoma
carcinoma
adjacent tissues
network
Microbiology
QR1-502
spellingShingle 16S rRNA
colorectal cancer
adenoma
carcinoma
adjacent tissues
network
Microbiology
QR1-502
Zongchao Mo
Peide Huang
Chao Yang
Sihao Xiao
Guojia Zhang
Fei Ling
Lin Li
Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue
description ABSTRACT As research focusing on the colorectal cancer fecal microbiome using shotgun sequencing continues, increasing evidence has supported correlations between colorectal carcinomas (CRCs) and fecal microbiome dysbiosis. However, large-scale on-site and off-site (surrounding adjacent) tissue microbiome characterization of CRC was underrepresented. Here, considering each taxon as a feature, we demonstrate a machine learning-based method to investigate tissue microbial differences among CRC, colorectal adenoma (CRA), and healthy control groups using 16S rRNA data sets retrieved from 15 studies. A total of 2,099 samples were included and analyzed in case-control comparisons. Multiple methods, including differential abundance analysis, random forest classification, cooccurrence network analysis, and Dirichlet multinomial mixture analysis, were conducted to investigate the microbial signatures. We showed that the dysbiosis of the off-site tissue of colonic cancer was distinctive and predictive. The AUCs (areas under the curve) were 80.7%, 96.0%, and 95.8% for CRC versus healthy control random forest models using stool, tissue, and adjacent tissue samples and 69.9%, 91.5%, and 89.5% for the corresponding CRA models, respectively. We also found that the microbiota ecologies of the surrounding adjacent tissues of CRC and CRA were similar to their on-site counterparts according to network analysis. Furthermore, based on the enterotyping of tissue samples, the cohort-specific microbial signature might be the crux in addressing classification generalization problems. Despite cohort heterogeneity, the dysbiosis of lesion-adjacent tissues might provide us with further perspectives in demonstrating the role of the microbiota in colorectal cancer tumorigenesis. IMPORTANCE Turbulent fecal and tissue microbiome dysbiosis of colorectal carcinoma and adenoma has been identified, and some taxa have been proven to be carcinogenic. However, the microbiomes of surrounding adjacent tissues of colonic cancerous tissues were seldom investigated uniformly on a large scale. Here, we characterize the microbiome signatures and dysbiosis of various colonic cancer sample groups. We found a high correlation between colorectal carcinoma adjacent tissue microbiomes and their on-site counterparts. We also discovered that the microbiome dysbiosis in adjacent tissues could discriminate colorectal carcinomas from healthy controls effectively. These results extend our knowledge on the microbial profile of colorectal cancer tissues and highlight microbiota dysbiosis in the surrounding tissues. They also suggest that microbial feature variations of cancerous lesion-adjacent tissues might help to reveal the microbial etiology of colonic cancer and could ultimately be applied for diagnostic and screening purposes.
format article
author Zongchao Mo
Peide Huang
Chao Yang
Sihao Xiao
Guojia Zhang
Fei Ling
Lin Li
author_facet Zongchao Mo
Peide Huang
Chao Yang
Sihao Xiao
Guojia Zhang
Fei Ling
Lin Li
author_sort Zongchao Mo
title Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue
title_short Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue
title_full Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue
title_fullStr Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue
title_full_unstemmed Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue
title_sort meta-analysis of 16s rrna microbial data identified distinctive and predictive microbiota dysbiosis in colorectal carcinoma adjacent tissue
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/319547ada5104d97b8e7ab82ab8369bb
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