Gut最新文献

{"title":"Unleashing the potential of exosome ncRNAs for early gastric cancer detection—a critical appraisal of machine learning approaches","authors":"Xuefan Zeng","doi":"10.1136/gutjnl-2025-334909","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334909","url":null,"abstract":"We read with great interest the article by Cai et al ,1 titled ‘Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study’, published in Gut . The study presents a novel approach for the early detection of gastric cancer (GC) using serum exosome non-coding RNAs (ncRNAs) and machine learning, which is a significant step forward in the field of liquid biopsy for cancer diagnostics. The study by Cai et al has several notable strengths. First, the comprehensive multi-cohort design, including both training and external validation cohorts, provides robust evidence for the diagnostic potential of the identified exosome ncRNA feature. The use of machine learning algorithms, particularly LASSO-logistic regression, to develop the combined diagnostic model (cd-score) is innovative and demonstrates high diagnostic accuracy with an area under the curve of 0.959 in the training cohort and 0.949 in the external validation cohort. Additionally, the study highlights the potential of DGCR9 as a therapeutic target, supported by in vitro and in vivo experiments. Despite these strengths, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"12 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Wnt signalling through LINC02418: insights from CRISPR screens","authors":"Zekiye Altan, Rory Johnson","doi":"10.1136/gutjnl-2024-334266","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334266","url":null,"abstract":"Colorectal cancer (CRC) remains highly challenging due to its complexity, high mortality rate and resistance to therapies. The development and progression of CRC are driven by complex interactions between genetic mutations and disruptions in epigenetic regulation.1 Among critical pathways involved, Wnt/β-catenin signalling plays a pivotal role by driving uncontrolled cell proliferation and maintaining cancer stem cell-like behaviour.2 Mutations in the APC gene frequently result in the hyperactivation of β-catenin-mediated transcriptional programmes3 (online supplemental figure 1A). While Wnt signalling represents a promising therapeutic target, its crucial role in normal tissue homeostasis complicates intervention, often leading to on-target toxicities.2 To address these challenges, in Gut, Schwarzmueller et al 4 applied cutting-edge RNA-based screening tools, including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) interference (CRISPRi) and Global Run-On Sequencing (GRO-seq), to identify tumour-specific vulnerabilities in CRC. Previous studies identified LINC02418 as an oncogenic regulator in CRC, acting primarily as a competing endogenous RNA (ceRNA).5 For instance, LINC02418 modulates oncogenic pathways by sponging miR-3619–5 p, thereby influencing the expression of targets such as MELK and contributing to tumour progression.6 While these findings highlight its role in CRC biology, Schwarzmueller et al provide evidence that LINC02418 is regulated, at least in part, by the Wnt/β-catenin pathway. This connection not only enhances our understanding of LINC02418’s function but also underscores its potential as a tumour-specific vulnerability, to selectively target CRC cells while sparing normal tissues. ### Supplementary data [gutjnl-2024-334266supp001.pdf] RNA-based therapies have become a transformative approach in oncology due to their capacity to target pathways previously considered to be undruggable.7 A significant benefit is their adaptability in addressing both traditional protein-coding genes (through their mRNA) and regulatory non-protein-coding RNAs like long non-coding RNA (lncRNAs), which, with their regulatory roles and tissue-specific expression, are valuable therapeutic targets in cancers with dysregulated gene expression.8 Although …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"18 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics analysis of immune correlatives in hepatocellular carcinoma patients treated with tremelimumab plus durvalumab.","authors":"Yuta Myojin, Sepideh Babaei, Rajiv Trehan, Christoph Hoffman, Noemi Kedei, Benjamin Ruf, Mohamed-Reda Benmebarek, Kylynda C Bauer, Patrick Huang, Chi Ma, Cecilia Monge, Changqing Xie, Donna Hrones, Austin G Duffy, Paul Armstrong, Lorenz Kocheise, Fiona Desmond, Jemma Buchalter, Marie Galligan, Colin Cantwell, Ronan Ryan, Jeff McCann, Michele Bourke, Ross Mac Nicholas, Ray McDermott, Joy Awosika, Maggie Cam, Rosanna Krebs, Anuradha Budhu, Mahler Revsine, William D Figg, David E Kleiner, Bernadette Redd, Bradford J Wood, Xin Wei Wang, Firouzeh Korangy, Manfred Claassen, Tim F Greten","doi":"10.1136/gutjnl-2024-334026","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334026","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC.</p><p><strong>Objective: </strong>To study immune responses in HCC patients treated with tremelimumab and durvalumab.</p><p><strong>Design: </strong>We treated 28 HCC patients with durvalumab, tremelimumab and locoregional therapies. We performed a high-dimensional multiomics analysis including whole exome sequencing, single-cell RNA seq, CO-Detection by indEXing, flow cytometry and multiplex cytokine/chemokine analysis of patients' blood and tumour samples and integrated this data to elucidate immune correlatives and response mechanisms. Mice with syngeneic HCC were treated with anti-PD-L1 plus anti-CTLA4 for hepatic lymphocytes, tumour-infiltrating lymphocytes and peripheral blood mononuclear cell analysis.</p><p><strong>Results: </strong>The median overall survival was 19.2 months. Tumour tissue analysis revealed enhanced interferon responses, with stronger effects in responders. Gene set variation analysis indicated enhanced antigen presentation in responders. Spatial analysis revealed that non-responder tumours had higher numbers of Tregs located in neighbourhoods enriched with immune cells and expressed higher levels of ICOS and PD-1. Conversely, non-responder PD1+CD8+T in these Treg-enriched neighbourhoods expressed lower ICOS. Cell-communication analysis demonstrated that Treg-CD8+T interaction was enhanced in non-responder tissue. Peripheral blood analysis showed increased classical monocytes in responders and Tregs in non-responders. Treg-CD8+T interaction was confirmed in preclinical models. Finally, single-patient computational analysis from the all-across analysis was performed on 860 features, which led to the identification of multiomics feature sets including Treg features.</p><p><strong>Conclusion: </strong>Our study provides a blueprint for in-depth analysis of immune correlates in immunotherapy studies and demonstrates the importance of Treg distribution in HCC.</p><p><strong>Trial registration numbers: </strong>NCT02821754 and the EudraCT identifier: 2019-002767-98.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of metachronous advanced neoplasia in patients with serrated lesions depending on follow-up schedule.","authors":"Juliette Labelle, Roupen Djinbachian, Heiko Pohl, Douglas K Rex, Edgard Medawar, Benoit Panzini, Mickael Bouin, Edmond-Jean Bernard, Daniel von Renteln","doi":"10.1136/gutjnl-2024-333681","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333681","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reparative immunological consequences of stem cell transplantation as a cellular therapy for refractory Crohn's disease.","authors":"Daniela Guisado, Sayali Talware, Xiaoli Wang, Andrew Davis, Elbek Fozilov, Aaron Etra, Jean-Frederic Colombel, Christoph Schaniel, Christopher Tastad, John E Levine, James L M Ferrara, Chuang Ling-Shiang, Ksenija Sabic, Shishir Singh, Bridget K Marcellino, Ronald Hoffman, Judy Cho, Louis Cohen","doi":"10.1136/gutjnl-2024-333558","DOIUrl":"10.1136/gutjnl-2024-333558","url":null,"abstract":"<p><strong>Background: </strong>Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown.</p><p><strong>Objective: </strong>The objective of this study is to understand how the immune system reconstitutes post-SCT and whether SCT may function as a cellular therapy restoring appropriately responsive immune cell populations from haematopoietic stem cells (HSCs).</p><p><strong>Design: </strong>Adults with CD with active clinical and endoscopic disease who failed available medical therapies were enrolled in a phase II study of SCT for refractory CD (n=19). Blood and intestinal samples were collected longitudinally and analysed using CyTOF and scRNA-seq. Stem cell autografts were functionally assayed in mouse xenograft models.</p><p><strong>Results: </strong>scRNA-seq and CyTOF analyses reveal that SCT predominantly affected the intestinal myeloid lineage with loss of inflammatory populations and return of macrophages capable of supporting mucosal healing. Xenograft models using patient HSCs suggested that HSCs support the early reconstitution of the myeloid lineage and reveal an impairment of short and long-term HSC engraftment that may determine SCT outcomes.</p><p><strong>Conclusions: </strong>This study suggests SCT functions as a myeloid-directed cellular therapy reinforcing the critical role of macrophages in refractory CD pathophysiology and as a target for cellular therapies. Furthermore, we report an unrecognised functional heterogeneity among HSC subpopulations in CD that may be relevant to our understanding of CD treatment and pathophysiology.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purified oat protein can trigger acute symptoms linked to immune activation in coeliac disease patients but not histological deterioration.","authors":"Melinda Y Hardy, Amy K Russell, Lee M Henneken, Greg Tanner, Ferenc Bekes, Ian Brown, Allan Motyer, Sam W Z Olechnowicz, Hugh H Reid, Jamie Rossjohn, Jason A Tye-Din","doi":"10.1136/gutjnl-2024-333589","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333589","url":null,"abstract":"<p><strong>Background: </strong>Oat ingestion in coeliac disease (CD) is generally regarded as safe but can trigger enteropathy and T cells specific for oat avenin in the gut and blood of some individuals.</p><p><strong>Objective: </strong>To correlate immune and clinical outcomes to oats, purified avenin and oat feeding studies were performed to examine symptoms, T-cell immunity and intestinal histology in CD.</p><p><strong>Design: </strong>33 treated HLA-DQ2.5+ adult CD patients underwent single-bolus or 6-week oat avenin or 3-month whole oats ingestion. T cell activation after avenin ingestion was measured using serum interleukin 2 (IL-2), a sensitive and specific biomarker of gluten-induced T cell activation and symptoms in CD. Symptom measures, intestinal histology, and immune studies on blood and duodenum were undertaken.</p><p><strong>Results: </strong>Among 29 CD participants, avenin induced dose-dependent T-cell activation in 11 (38%) and acute symptoms in 17 (59%). Higher IL-2 levels correlated with more severe symptoms. A single highly symptomatic patient vomited in response to avenin (1/29; 3%) and exhibited a striking pro-inflammatory cytokine profile similar to wheat-induced responses. Avenin increased the frequency of CD38-expressing tetramer+integrin β7+ T effector memory CD4+ T cells in the blood, however symptoms, IL-2 release and tetramer frequency fell following 6-week avenin intake and no enteropathy was observed.</p><p><strong>Conclusion: </strong>Gluten-contamination-free oats can trigger acute dose-dependent immune and symptom responses but usually at a level insufficient to cause sustained symptoms or enteropathy. In 1 of 29 (3%) participants, oat avenin triggered a pro-inflammatory wheat-like response, highlighting that a minority of CD patients may need to exclude oats. Informed choice regarding oats ingestion in CD is important.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Putting the best foot forward: rethinking the paradigms in ASUC.","authors":"Shaji Sebastian, Vineet Ahuja, Ajit Sood","doi":"10.1136/gutjnl-2024-334267","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334267","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-microbiome determinants of insulin resistance in obesity: alone we go faster, together we go further!","authors":"Andre Marette, Genevieve Pilon","doi":"10.1136/gutjnl-2024-333855","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333855","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global health inequalities in the burden of gastrointestinal cancers from 1990 to 2021.","authors":"Chunlong Liu, Ziqiang He, Jiangtao Yu, Rui Yang","doi":"10.1136/gutjnl-2025-334802","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334802","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It takes two to TAM-go.","authors":"Eduardo Garvin-Jiménez, María Casanova-Acebes","doi":"10.1136/gutjnl-2024-334506","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334506","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}