FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3160848279> ?p ?o ?g. }

• W3160848279 abstract "Abstract Objective Transcriptomic-based subtyping, Consensus Molecular Subtyping (CMS) and CRC Intrinsic Subtyping (CRIS), identify a patient subpopulation with mesenchymal traits (CMS4/CRIS-B) and poorer outcome. Here, we investigated the relationship between prevalence of Fusobacterium nucleatum ( Fn ) and Fusobacteriales , CMS/CRIS subtyping, cell type composition, immune infiltrates and host contexture to refine patients stratification and identify druggable context-specific vulnerabilities. Design We coupled cell culture experiments with characterization of Fn / Fusobacteriales prevalence and host biology/microenviroment in tumours from 2 independent CRC patient cohorts (Taxonomy: n=140; TCGA-COAD-READ: n=605). Results In vitro, Fn infection induced inflammation via NFκB/TNFα in HCT116 and HT29 cancer cell lines. In patients, high Fn / Fusobacteriales were found in CMS1, MSI tumours, with infiltration of macrophages M1, reduced macrophages M2, and high IL6/IL8/IL1β signaling. Analysis of the Taxonomy cohort suggested that Fn was prognostic for CMS4/CRIS-B patients, despite having lower Fn load than CMS1 patients. In the TCGA-COAD-READ cohort, we likewise identified a differential association between Fusobacteriales relative abundance and outcome when stratifying patients in mesenchymal (either CMS4 and/or CRIS-B) vs. non-mesenchymal (neither CMS4 nor CRIS-B). Patients with mesenchymal tumours and high Fusobacteriales had approximately 2-fold higher risk of worse outcome. These associations were null in non-mesenchymal patients. Modelling the 3-way association between Fusobacteriales prevalence, molecular subtyping, and host contexture with logistic models with an interaction term disentangled the pathogen/host-signaling relationship and identified aberrations (including EMT/WNT/NOTCH) as candidate targets. Conclusion This study identifies CMS4/CRIS-B patients with high Fn / Fusobacteriales prevalence as a high-risk subpopulation that may benefit from therapeutics targeting mesenchymal biology. Significance of this study What is already known on this subject? Fusobacterium nucleatum ( Fn ), a commensal Gram-negative anaerobe from the Fusobacteriales order, is an onco-bacterium in CRC as a causal relationship between Fn prevalence and CRC pathogenesis, progression and treatment response has been reported in vivo . Broad spectrum antibiotics has proven moderately successful in reducing tumour growth in preclinical models. However, the use of antibiotics to treat bacterium-positive cases in the clinic is not a viable option as it may further alter the already dysbiotic gut microbiome of CRC patients and may also have limited efficacy against Fn which penetrates and embeds deeply within the tumour. The highly heterogenous CRC patient population can be classified into distinct molecular subtypes (CMS and CRIS) based on gene expression profiles mirroring the underlying transcriptional programs. Patients classified as CMS4 and CRIS-B exhibit a mesenchymal phenotype and have poorer outcome. What are the new findings? Fn / Fusobacteriales prevalence is associated with immune involvement (decrease in macrophages M1 and increase in macrophages M2) and activation of specific signalling programs (inflammation, DNA damage, WNT, metastasis, proliferation, cell cycle) in the host tumours. The prevalence of bacteria from the Fusobacteriales order, largely driven by Fn species, play an active or opportunistic role depending on the underlying host tumour biology and microenvironment. Fn and other species of the Fusobacteriales order are enriched in CMS1 (immuno, microsatellite unstable) patients compared to CMS2-4 cases. Fn / Fusobacteriales prevalence is associated with worse clinical outcome in patients with mesenchymal-rich CMS4/CRIS-B tumours, but not in patients with other molecular subtypes. How might it impact on clinical practice in the foreseeable future? Fn / Fusobacteriales screening and transcriptomic-based molecular subtyping should be considered to identify patients with mesenchymal-rich tumours and high bacterium prevalence and to inform disease management. Fn / Fusobacteriales prevalence may need to be addressed exclusively in patients with mesenchymal-rich high-stromal infiltrating tumours rather than a blanket-approach to treat all pathogen-positive patients. Clinical management of the disease for this subpopulation of high-risk patients with unfavourable clinical outcome could be attained by administering compounds currently in clinical trials that target aberrations in the host signaling pathways (NOTCH, WNT, EMT) and tumour microenviroment (inflammasome, activated T cells, complement system, and macrophage chemotactism and activation)." @default.
• W3160848279 created "2021-05-24" @default.
• W3160848279 creator A5042357980 @default.
• W3160848279 creator A5046562303 @default.
• W3160848279 creator A5058174847 @default.
• W3160848279 creator A5066581807 @default.
• W3160848279 creator A5068105834 @default.
• W3160848279 creator A5078841356 @default.
• W3160848279 date "2021-05-18" @default.
• W3160848279 modified "2023-10-06" @default.
• W3160848279 title "Patients with mesenchymal tumours and high <i>Fusobacteriales</i> prevalence have worse prognosis in colorectal cancer (CRC)" @default.
• W3160848279 cites W1568216332 @default.
• W3160848279 cites W1896348045 @default.
• W3160848279 cites W1934094702 @default.
• W3160848279 cites W1995474832 @default.
• W3160848279 cites W2002797634 @default.
• W3160848279 cites W2034992352 @default.
• W3160848279 cites W2039084641 @default.
• W3160848279 cites W2095269215 @default.
• W3160848279 cites W2096139589 @default.
• W3160848279 cites W2107097628 @default.
• W3160848279 cites W2108373994 @default.
• W3160848279 cites W2111282720 @default.
• W3160848279 cites W2135201496 @default.
• W3160848279 cites W2136070771 @default.
• W3160848279 cites W2140679462 @default.
• W3160848279 cites W2157852151 @default.
• W3160848279 cites W2169281418 @default.
• W3160848279 cites W2470602494 @default.
• W3160848279 cites W2533508881 @default.
• W3160848279 cites W2584619074 @default.
• W3160848279 cites W2617865703 @default.
• W3160848279 cites W2746252349 @default.
• W3160848279 cites W2768799378 @default.
• W3160848279 cites W2788975052 @default.
• W3160848279 cites W2797068438 @default.
• W3160848279 cites W2800376069 @default.
• W3160848279 cites W2808042645 @default.
• W3160848279 cites W2883814206 @default.
• W3160848279 cites W2885201462 @default.
• W3160848279 cites W2886432340 @default.
• W3160848279 cites W2889646458 @default.
• W3160848279 cites W2898606030 @default.
• W3160848279 cites W2901123261 @default.
• W3160848279 cites W2904988746 @default.
• W3160848279 cites W2947548345 @default.
• W3160848279 cites W2947554843 @default.
• W3160848279 cites W2950036522 @default.
• W3160848279 cites W2966140584 @default.
• W3160848279 cites W2967952009 @default.
• W3160848279 cites W2972846551 @default.
• W3160848279 cites W2975952731 @default.
• W3160848279 cites W2976561454 @default.
• W3160848279 cites W3000043266 @default.
• W3160848279 cites W3017957088 @default.
• W3160848279 cites W3031230415 @default.
• W3160848279 cites W3035917003 @default.
• W3160848279 cites W3036446761 @default.
• W3160848279 cites W3045284805 @default.
• W3160848279 cites W3131096504 @default.
• W3160848279 cites W3132259578 @default.
• W3160848279 cites W3134165232 @default.
• W3160848279 cites W4235998362 @default.
• W3160848279 doi "https://doi.org/10.1101/2021.05.17.444326" @default.
• W3160848279 hasPublicationYear "2021" @default.
• W3160848279 type Work @default.
• W3160848279 sameAs 3160848279 @default.
• W3160848279 citedByCount "3" @default.
• W3160848279 countsByYear W31608482792022 @default.
• W3160848279 countsByYear W31608482792023 @default.
• W3160848279 crossrefType "posted-content" @default.
• W3160848279 hasAuthorship W3160848279A5042357980 @default.
• W3160848279 hasAuthorship W3160848279A5046562303 @default.
• W3160848279 hasAuthorship W3160848279A5058174847 @default.
• W3160848279 hasAuthorship W3160848279A5066581807 @default.
• W3160848279 hasAuthorship W3160848279A5068105834 @default.
• W3160848279 hasAuthorship W3160848279A5078841356 @default.
• W3160848279 hasBestOaLocation W31608482791 @default.
• W3160848279 hasConcept C104317684 @default.
• W3160848279 hasConcept C121608353 @default.
• W3160848279 hasConcept C126322002 @default.
• W3160848279 hasConcept C137620995 @default.
• W3160848279 hasConcept C143998085 @default.
• W3160848279 hasConcept C198826908 @default.
• W3160848279 hasConcept C199360897 @default.
• W3160848279 hasConcept C41008148 @default.
• W3160848279 hasConcept C502942594 @default.
• W3160848279 hasConcept C526805850 @default.
• W3160848279 hasConcept C54355233 @default.
• W3160848279 hasConcept C71924100 @default.
• W3160848279 hasConcept C83852419 @default.
• W3160848279 hasConcept C86803240 @default.
• W3160848279 hasConceptScore W3160848279C104317684 @default.
• W3160848279 hasConceptScore W3160848279C121608353 @default.
• W3160848279 hasConceptScore W3160848279C126322002 @default.
• W3160848279 hasConceptScore W3160848279C137620995 @default.
• W3160848279 hasConceptScore W3160848279C143998085 @default.
• W3160848279 hasConceptScore W3160848279C198826908 @default.
• W3160848279 hasConceptScore W3160848279C199360897 @default.
• W3160848279 hasConceptScore W3160848279C41008148 @default.

• next