Differences in the On- and Off-Tumor Microbiota between Right- and Left-Sided Colorectal Cancer

Microorganisms, Journal Year: 2021, Volume and Issue: 9(5), P. 1108 - 1108

Published: May 20, 2021

This study aims to determine differences in the on- and off-tumor microbiota between patients with right- left-sided colorectal cancer. Microbiome profiling of tumor tumor-adjacent biopsies from right-sided (n = 17) 7) adenocarcinoma was performed using 16S ribosomal RNA sequencing. Off-tumor alpha beta diversity were significantly different cancer patients. However, no on-tumor observed locations. Comparing showed right colon be enriched species Lachnoclostridium, Selenomonas, Ruminococcus genera. Whereas left is Epsilonbacteraeota phylum, Campylobacteria class, Pasteurellales Campylobacterales orders, contrast, relatively fewer bacterial taxonomy sites, tumors being Methylophilaceae Vadin BE97 families Alloprevotella, Intestinibacter, Romboutsia, 2 Patients had large taxonomic their paired microbiota, while differences. Collectively, this suggests that show distinctive populations; however, presence a colonic leads more consistent

Language: Английский

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HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

British Journal of Cancer, Journal Year: 2022, Volume and Issue: 126(12), P. 1783 - 1794

Published: Feb. 17, 2022

Abstract Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed identifying BTC-specific DNA methylation alterations. Methods Study design included statistical power and sample size estimation. A genome-wide study of an explorative cohort (50 BTC ten matched non-tumoral tissue samples) has been performed. altered CpG islands were validated in over 180 samples (174 BTCs 13 controls). The final biomarkers, selected by a machine-learning approach, independent (18 BTCs, 14 bile (24 five replication series, using droplet digital PCR. Results We identified successfully alterations 200 samples. two-biomarker panel, in-house algorithm, showed AUC > 0.97. best-performing biomarker (chr2:176993479-176995557), associated HOXD8 , pivotal gene cancer-related pathways, achieved 100% sensitivity specificity new series Conclusions novel fully efficient biomarker, gene, detectable both standardised assay ready-to-use clinical trials also including from non-invasive matrices.

Language: Английский

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Comprehensive analysis of alternative splicing across multiple transcriptomic cohorts reveals prognostic signatures in prostate cancer

Human Genomics, Journal Year: 2023, Volume and Issue: 17(1)

Published: Nov. 3, 2023

Abstract Background Alternative splicing (AS) plays a crucial role in transcriptomic diversity and is hallmark of cancer that profoundly influences the development progression prostate (PCa), prevalent potentially life-limiting among men. Accumulating evidence has highlighted association between AS dysregulation onset PCa. However, comprehensive integrative analysis profiles at event level, utilising data from multiple high-throughput cohorts evaluating prognosis PCa progression, remains lacking calls for thorough exploration. Results We identified differentially expressed retained intron ZWINT across three distinct cohorts, encompassing an original array-based dataset profiled by us previously two RNA sequencing (RNA-seq) datasets. Subsequent in-depth analyses these RNA-seq datasets revealed 141 altered events, which 21 demonstrated significant with patients’ biochemical recurrence-free survival (BCRFS). formulated event-based prognostic signature, capturing six pivotal events genes CYP4F12 , NFATC4 PIGO CYP3A5 ALS2CL FXYD3 . This signature effectively differentiated high-risk patients diagnosed PCa, who experienced shorter BCRFS, their low-risk counterparts. Notably, signature's predictive power surpassed traditional clinicopathological markers forecasting 5-year demonstrating robust performance both internal external validation sets. Lastly, we constructed novel nomogram integrates Gleason scores pathological tumour stages, improved prognostication BCRFS. Conclusions Prediction clinical elusive research uncovers associated augmenting existing tools, thus refining decision-making.

Language: Английский

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Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy

Gut, Journal Year: 2024, Volume and Issue: unknown, P. gutjnl - 332193

Published: Sept. 9, 2024

Background Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. Objective We aimed to characterise the differences between adenomas (ADs) representing early stage of colonic tumourigenesis. Design Single-cell spatial transcriptomic datasets were analysed reveal alterations colon ADs. Cells, animal experiments clinical specimens used verify results. Results analysis revealed that ADs, there was a significant reduction goblet cells, these cells dysfunctional with attenuated mucin biosynthesis defective antigen presentation. An impairment mucus barrier led biofilm formation crypts subsequent bacteria invasion into The regions spatially surrounding occupation underwent an inflammatory response by lipopolysaccharide (LPS) apoptosis process, as transcriptomics. A S100A11 + epithelial cell population ADs identified, its expression level induced bacterial LPS peptidoglycan. facilitated tumour growth syngeneic immunocompetent mice increased myeloid-derived suppressor (MDSC) but reduced cytotoxic CD8+ T cells. Targeting well-tolerated antagonists receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired MDSC infiltration, thereby boosting efficacy anti-programmed death protein 1 therapy cancer. Conclusion Our findings unravelled consequential translocation activated S100A11-RAGE axis which recruits MDSCs promote immune evasion. this Azeliragon improves immunotherapy

Language: Английский

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Right colon, left colon, and rectal cancer have different oncologic and quality of life outcomes

International Journal of Colorectal Disease, Journal Year: 2022, Volume and Issue: 37(4), P. 939 - 948

Published: March 21, 2022

Language: Английский

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Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 11, 2023

Introduction Characterization of the tumour immune infiltrate (notably CD8+ T-cells) has strong predictive survival value for cancer patients. Quantification CD8 T-cells alone cannot determine antigenic experience, as not all infiltrating recognize antigens. Activated tumour-specific tissue resident memory (T RM ) can be defined by co-express CD103, CD39 and CD8. We investigated hypothesis that abundance localization T provides a higher-resolution route to patient stratification. Methods A comprehensive series 1000 colorectal (CRC) were arrayed on microarray, with representative cores from three locations adjacent normal mucosa. Using multiplex immunohistochemistry we quantified determined . Results Across patients, activated an independent predictor survival, superior alone. Patients best had immune-hot tumours heavily infiltrated throughout Interestingly, differences between right- left-sided apparent. In CRC, only presence (and alone) was prognostically significant. low numbers cells poor prognosis even high T-cell infiltration. contrast, in right-sided infiltration good prognosis. Conclusion The intra-tumoural is CRC potentially risks under treatment Measuring both tumour-associated total disease potential minimize current under-treatment challenge will design immunotherapies, patients activate RM, result effective responses thereby improve survival.

Language: Английский

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Diferencias en factores de riesgo, características demográficas y clínico-patológicas al diagnóstico entre el cáncer de colon proximal y distal: un análisis multicéntrico de cohorte retrospectiva

Revista de Gastroenterología de México, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

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Identification of SRC, AKT1 and MAPK3 as Therapeutic Targets of Apigenin and Luteolin in Colorectal and Colon Carcinoma through Network Pharmacology

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106313 - 106313

Published: March 1, 2025

Language: Английский

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DIVERT-Ca: unveiling the hidden link between acute diverticulitis and colorectal cancer risk—multicentre retrospective study

International Journal of Colorectal Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: March 15, 2025

Abstract Introduction Colorectal cancer (CRC) is the third most common worldwide, accounting for approximately 10% of all malignancies. Emerging trends association with risk factors such as diverticulitis highlight need updated screening and follow-up protocols. We aimed to examine associated development CRC within 12 months following an episode acute diverticulitis, identify areas streamline follow-up. Methods performed a retrospective multicentre study adult patients admitted in 2022 computed tomography (CT) confirmed across four large NHS Trusts UK. Patient demographics, comorbidities, clinical presentation, vital signs, laboratory results, details in-patient stay, investigations were collected analysed. Our primary outcome was incidence index presentation diverticulitis. Analysed secondary outcomes potential patient diagnosis All statistical analysis using R (version 4.4) P -values < 0.05 considered statistically significant. Results A total 542 over period included. The median age our cohort 62 (51–73) years, 204 (37.6%) male. Ten (1.8%) diagnosed 12-month period. Hinchey grade Ib significantly (OR 4.51, = 0.028). Colonoscopic requests between 40 60 mild white cell count (WCC) elevation, hospital stay 3–7 days. Male gender, 18 elevated C-reactive protein (CRP) strongly but not Follow-up inconsistent 53.7% having luminal investigations. Conclusion in-keeping published literature. 1b subsequent diagnosis. These findings emphasise specialised radiological review CT scans detect underlying malignancy. Moreover, standardised protocols are needed avoid missing malignant lesions.

Language: Английский

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Serum Protein Profiling as theranostic biomarkers for Left- and Right-Sided Colon Cancer using Luminex ^® technology

Cancer Biomarkers, Journal Year: 2025, Volume and Issue: 42(4)

Published: April 1, 2025

Background Given the differences between malignancies arising from different segments of colon, specific theranostic biomarkers can be linked to either Right-sided (RCC) or Left-sided colon cancer (LCC). Objective Analysis 65 serum proteins identify panels for LCC and RCC. Methods Serum levels immunomodulators were measured in CC, LCC, RCC patients, as well healthy controls with ProcartaPlex Human Immune Monitoring 65-Plex Panel. Results IL-27 may used early detection LCC. CD-30 was up-regulated metastatic BLC CD-40L down-regulated MDC MMP-1 positively associated, while IL-9 VEGF-A negatively associated lymph nodes invasion CC. Up-regulation IL-12p70 contrasted down-regulation MIP-1beta. IL-23, I-TAC, SDF-1α resistant CC Folfox chemotherapy, I-TAC IL-2 FGF-2 down-regulated, APRIL Conclusions Our study revealed significant protein emphasizing importance explore novel resistance sensitivity chemotherapy.

Language: Английский

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