A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer

From BugSigDB
Reviewed Marked as Reviewed by Fatima on 2022/09/7
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yuan D, Tao Y, Wang H, Wang J, Cao Y, Cao W, Pan S, Yu Z
Journal
Investigational new drugs
Year
2022
Keywords:
16S, Colorectal cancer, Driver gene mutation, Microbiota, Target therapy
Studies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. For 39 of the CRC patients, targeted Next Generation Sequencing (NGS) was carried out at formalin fixed paraffin embedded (FFPE) samples to identify somatic mutation profiles. Compared to the HC group, the microbial diversity of CRC patients was significantly lower. In the CRC group, we found a microbiome that was significantly enriched for strains of Bifidobacterium, Bacteroides, and Megasphaera whereas in the HC group the abundance of Collinsella, Faecalibacterium, and Agathobacter strains was higher. Among the mutations detected in the CRC group, the APC gene had the highest mutation rate (77%, 30/39). We found that the KRAS mutant type was closely associated with Faecalibacterium, Roseburia, Megamonas, Lachnoclostridium, and Harryflintia. Notably, Spearman correlation analysis showed that KRAS mutations were negatively correlated with the existence of Bifidobacterium and positively correlated with Faecalibacterium. By employing 16S rRNA gene sequencing, we identified more unique features of microbiota profiles in CRC patients. For the first time, our study showed that gene mutations could directly be linked to the microbiota composition of CRC patients. We hypothesize that the effect of a targeted colorectal cancer therapy is also closely related to the colorectal flora, however, this requires further investigation.

Experiment 1


Reviewed Marked as Reviewed by Fatima on 2022/10/20

Curated date: 2022/08/28

Curator: Mary Bearkland

Revision editor(s): WikiWorks, Fatima, Rimsha, Mary Bearkland, Peace Sandy

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
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,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Colorectal adenocarcinoma adenocarcinoma of large bowel,adenocarcinoma of large intestine,adenocarcinoma of the large bowel,adenocarcinoma of the large intestine,colorectal (colon or rectal) adenocarcinoma,colorectal adenocarcinoma,colorectum adenocarcinoma,large bowel adenocarcinoma,large intestine adenocarcinoma,Colorectal adenocarcinoma
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
colorectal cancer patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
diagnosed of colorectal cancer by colonoscopy and histopathology
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
44
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/10/20

Curated date: 2022/08/29

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figures 4b

Description: Fig. 4 Difference of fecal microbiota in CRC patients and HC. b. LDA score computed from features differentially abundant in CRC and HC fecal samples. The criteria for feature selection were LDA score > 4, p < 0.05, Green and red represent the HC group and CRC group, respectively.

Abundance in Group 1: increased abundance in colorectal cancer patients

NCBI Quality ControlLinks
Bacteroides
Bifidobacterium
Shigella
Escherichia

Revision editor(s): Mary Bearkland

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/10/20

Curated date: 2022/08/29

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Fatima

Source: Figures 4b

Description: Fig. 4 Difference of fecal microbiota in CRC patients and HC. b. LDA score computed from features differentially abundant in CRC and HC fecal samples. The criteria for feature selection were LDA score > 4, p < 0.05, Green and red represent the HC group and CRC group, respectively.

Abundance in Group 1: decreased abundance in colorectal cancer patients

NCBI Quality ControlLinks
Collinsella
Coprobacillus
Faecalibacterium
Romboutsia
Streptococcus
Agathobacter

Revision editor(s): Mary Bearkland, Fatima

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2022/10/20

Curated date: 2022/08/28

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Fatima, LGeistlinger, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
colorectal cancer patients without KRAS mutation
Group 1 name Corresponds to the case (exposed) group for case-control studies
colorectal cancer patients with KRAS mutation
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
18
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
No antibiotics for one month prior to surgery (fecal sample was taken the night before surgery)

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
Not specified


Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/10/20

Curated date: 2022/08/31

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Fatima, Merit

Source: Figure 5a

Description: LEfSe was used to compare the microbial variation of the KRAS

Abundance in Group 1: increased abundance in colorectal cancer patients with KRAS mutation

NCBI Quality ControlLinks
Acidaminococcaceae
Alistipes sp.
Anaerobutyricum hallii
Bacillota
Butyricicoccus
Caproiciproducens
Enterocloster bolteae
Faecalibacterium
Gracilibacter
Harryflintia
Harryflintia acetispora
Holdemania filiformis
Lachnoclostridium
Lachnoclostridium edouardi
Lachnospiraceae
Megamonas
Novosphingobium
Phascolarctobacterium
Roseburia
Roseburia sp. 11SE38
Sphingomonadaceae
Sphingomonadales
unclassified Anaerobutyricum
unclassified Butyricicoccus
unclassified Caproiciproducens
unclassified Coprococcus
unclassified Faecalibacterium
unclassified Megamonas
unclassified Phascolarctobacterium
uncultured Eubacterium sp.
uncultured Gracilibacter sp.
uncultured Prevotella sp.

Revision editor(s): Mary Bearkland, Fatima, Merit

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/10/20

Curated date: 2022/08/31

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Fatima

Source: Figure 5a

Description: LEfSe was used to compare the microbial variation of the KRAS

Abundance in Group 1: decreased abundance in colorectal cancer patients with KRAS mutation

NCBI Quality ControlLinks
Actinomycetota
Bacteria
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Bifidobacterium dentium
Bifidobacterium longum
Bifidobacterium pseudocatenulatum
Enterobacterales
Enterobacteriaceae
Lactobacillus sp. T17/4F
uncultured Bifidobacterium sp.
Bifidobacterium catenulatum subsp. kashiwanohense

Revision editor(s): Mary Bearkland, Fatima

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/02

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
colorectal cancer patients without TP53 mutation
Group 1 name Corresponds to the case (exposed) group for case-control studies
colorectal cancer patients with TP53 mutation
Group 0 sample size Number of subjects in the control (unexposed) group
11
Group 1 sample size Number of subjects in the case (exposed) group
28

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/02

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 5b

Description: LEfSe was used to compare the microbial variation of the TP53

Abundance in Group 1: increased abundance in colorectal cancer patients with TP53 mutation

NCBI Quality ControlLinks
Eubacterium coprostanoligenes

Revision editor(s): Mary Bearkland

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/02

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Merit, Atrayees

Source: Figure 5b

Description: LEfSe was used to compare the microbial variation of the TP53

Abundance in Group 1: decreased abundance in colorectal cancer patients with TP53 mutation

NCBI Quality ControlLinks
Oscillospiraceae
unclassified Oscillospiraceae

Revision editor(s): Mary Bearkland, Merit, Atrayees

Experiment 4


Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/02

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
colorectal cancer patients without APC mutation
Group 1 name Corresponds to the case (exposed) group for case-control studies
colorectal cancer patients with APC mutation
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
diagnosed with colorectal cancer by colonoscopy and histopathology
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/03

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 5c

Description: LEfSe was used to compare the microbial variation of the APC groups.

Abundance in Group 1: increased abundance in colorectal cancer patients with APC mutation

NCBI Quality ControlLinks
Actinomyces
Actinomycetaceae
Actinomycetales

Revision editor(s): Mary Bearkland

Experiment 5


Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/02

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
colorectal cancer patients without PIK3CA mutation
Group 1 name Corresponds to the case (exposed) group for case-control studies
colorectal cancer patients with PIK3CA mutation
Group 0 sample size Number of subjects in the control (unexposed) group
33
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/03

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 5d

Description: LEfSe was used to compare the microbial variation of the PIK3CA groups.

Abundance in Group 1: decreased abundance in colorectal cancer patients with PIK3CA mutation

NCBI Quality ControlLinks
Actinomycetales
unclassified Actinomyces
Actinomycetaceae
Actinomyces

Revision editor(s): Mary Bearkland

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-19

Curated date: 2022/09/03

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, Fatima

Source: Figure 5d

Description: LEfSe was used to compare the microbial variation of the PIK3CA groups.

Abundance in Group 1: increased abundance in colorectal cancer patients with PIK3CA mutation

NCBI Quality ControlLinks
Alistipes
Bifidobacterium catenulatum
Desulfovibrio sp. LNB2
Enterobacter sp. enrichment culture clone HSL70
Lactobacillus
Megasphaera
Moryella indoligenes
Negativicutes
Ralstonia
Selenomonadales
Veillonellaceae
unclassified Megasphaera
unclassified Ralstonia
uncultured Selenomonas sp.
Lactobacillaceae

Revision editor(s): Mary Bearkland, Fatima