Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy

Study information

Reviewed Marked as Reviewed by Fatima on 2022/07/25

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

28753429

DOI Digital object identifier for electronic documents.

10.1016/j.cell.2017.07.008

URI

Authors

Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, Qian Y, Kryczek I, Sun D, Nagarsheth N, Chen Y, Chen H, Hong J, Zou W, Fang JY

Journal

Cell

Year

2017

Keywords:

Colorectal cancer, F.nucleatum, Toll-like receptor, autophagy, chemoresistance, miRNA, recurrence

Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/07/25

Curated date: 2022/06/04

Curator: Jeshudy

Revision editor(s): Jeshudy, WikiWorks, 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: Intestine Bowel,Intestinal tract,Intestine

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: Patients without CRC recurrence

Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with CRC recurrence

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patient tissues with colorectal cancer recurrence

Group 0 sample size Number of subjects in the control (unexposed) group: 16

Group 1 sample size Number of subjects in the case (exposed) group: 15

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 6 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V3

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3.5

Signature 1

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Curated date: 2022/06/04

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 1B

Description: (B) Linear discriminant analysis (LDA) coupled with the effect size measurements identifies the significant abundance of data in A. Taxa enriched in recurrent (Red) and non-recurrent (Blue) patients are indicated with negative (Red) or positive (Blue) LDA scores, respectively. Only taxa greater than LDA threshold of 3.5 are shown.

Abundance in Group 1: increased abundance in Patients with CRC recurrence

NCBI	Quality Control	Links
Fusobacterium
Parvimonas
Anaerobacterium
Peptostreptococcus
Prevotella

Revision editor(s): Jeshudy

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/07/25

Curated date: 2022/06/04

Curator: Jeshudy

Revision editor(s): Jeshudy

Source: Figure 1B

Description: Linear discriminant analysis (LDA) coupled with the effect size measurements identifies the significant abundance of data in A. Taxa enriched in recurrent (Red) and non-recurrent (Blue) patients are indicated with negative (Red) or positive (Blue) LDA scores, respectively. Only taxa greater than LDA threshold of 3.5 are shown.

Abundance in Group 1: decreased abundance in Patients with CRC recurrence

NCBI	Quality Control	Links
Stenotrophomonas
Veillonella

Revision editor(s): Jeshudy