Dataset Information

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis.

ABSTRACT:

Background

Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.

Methods

We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.

Results

F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations.

Conclusions

F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.

Impact

Our findings identify the F. nucleatum subspecies animalis as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.

SUBMITTER: Borozan I

PROVIDER: S-EPMC8755593 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with <i>Fusobacterium nucleatum</i> and Its Subspecies <i>animalis</i>.

Borozan Ivan I Zaidi Syed H SH Harrison Tabitha A TA Phipps Amanda I AI Zheng Jiayin J Lee Stephen S Trinh Quang M QM Steinfelder Robert S RS Adams Jeremy J Banbury Barbara L BL Berndt Sonja I SI Brezina Stefanie S Buchanan Daniel D DD Bullman Susan S Cao Yin Y Farris Alton B AB Figueiredo Jane C JC Giannakis Marios M Heisler Lawrence E LE Hopper John L JL Lin Yi Y Luo Xuemei X Nishihara Reiko R Mardis Elaine R ER Papadopoulos Nickolas N Qu Conghui C Reid Emma E G EEG Thibodeau Stephen N SN Harlid Sophia S Um Caroline Y CY Hsu Li L Gsur Andrea A Campbell Peter T PT Gallinger Steven S Newcomb Polly A PA Ogino Shuji S Sun Wei W Hudson Thomas J TJ Ferretti Vincent V Peters Ulrike U

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20211104 1

<h4>Background</h4><i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.<h4>Methods</h4>We characterized <i>F. nucleatum</i> and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of <i>nusA</i>, <i>nusG</i>, and bacterial <i>16s rRNA</i> genes in tumors from 1,994 patients with colorectal ...[more]

PMID: 34737207

Similar Datasets

Project description:ImportanceEvidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity.ObjectiveTo test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue.Design, setting, and participantsA cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing.Main outcomes and measuresDensities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis.ResultsF nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with F nucleatum-negative cases, F nucleatum-high cases were inversely associated with the density of CD3+ T cells (for a unit increase in quartile categories of CD3+ T cells as an outcome: multivariable odds ratio, 0.47 [95% CI, 0.26-0.87]; P for trend = .006). The amount of F nucleatum was not significantly associated with the density of CD8+, CD45RO+, or FOXP3+ T cells (P fortrend = .24, .88, and .014, respectively).Conclusions and relevanceThe amount of tissue F nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue. On validation, our human population data may provide an impetus for further investigations on potential interactive roles of Fusobacterium and host immunity in colon carcinogenesis.

Dataset Information

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis.

Background

Methods

Results

Conclusions

Impact

Publications

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with <i>Fusobacterium nucleatum</i> and Its Subspecies <i>animalis</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis.

Background

Methods

Results

Conclusions

Impact

Publications

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; and Its Subspecies &lt;i&gt;animalis&lt;/i&gt;.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with <i>Fusobacterium nucleatum</i> and Its Subspecies <i>animalis</i>.