Gut最新文献

{"title":"Underwater endoscopic submucosal dissection for large non-pedunculated colorectal polyps","authors":"Roberto de Sire, Antonio Capogreco, Davide Massimi, Ludovico Alfarone, Luca Brandaleone, Vincenzo Vadalà, Francesco Minini, Spadaccini Marco, Antonio Facciorusso, Asma Alkandari, Pradeep Bhandari, Cesare Hassan, Roberta Maselli, Alessandro Repici","doi":"10.1136/gutjnl-2025-334995","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334995","url":null,"abstract":"Underwater endoscopic resections have emerged as promising alternatives to the conventional techniques for the treatment of large (≥2 cm) non-pedunculated colorectal polyps; this may also apply to colorectal endoscopic submucosal dissection (ESD) using saline. This retrospective study uses a propensity score-matched analysis of 82/208 such lesions treated during a 3-year period. Underwater ESD using saline improved R0 resection rates (97.6% vs 82.9%), enhanced dissection speed (31.8 mm2/min vs 22.9 mm2/min) and reduced the use of haemostatic forceps for intraprocedural bleeding (0% vs 14.6%). We recommend this technique to be adopted to facilitate ESD for large non-pedunculated colorectal lesions. ESD is a preferred technique for en bloc resection of large (≥2 cm) non-pedunculated colorectal polyps or adenomas, offering high R0 resection and low recurrence rates.1 2 However, its adoption in Western countries remains limited due to technical complexity, long procedure times and associated adverse events.3 Underwater ESD, which replaces CO2 insufflation with a saline-filled environment, has been proposed to enhance visualisation, traction and submucosal dissection, improving procedural outcomes.4–6 Additionally, saline impedance allows prophylactic underwater vessel coagulation when swift coagulation (effect: 4.0; electrosurgical generator: VIO3, Erbe Elektromedizin GmbH) is applied, improving submucosal vessel sealing to reduce intraprocedural bleeding.7–10 This retrospective study included all consecutive large non-pedunculated colorectal adenomas treated by ESD from January 2021 to December 2023. Underwater ESD using saline was gradually and systematically implemented after January 2023. Eligible participants were adults aged 18 years or older with large lesions (≥2 cm). Exclusion criteria were treatment by endoscopic mucosal resection, need for deeper resection (endoscopic intermuscular dissection or endoscopic full-thickness resection), or surgery, suspected sessile serrated lesions, inability to suspend anticoagulant therapy or to provide informed consent. Relevant clinical and endoscopic data were systematically collected in an electronic database. The procedures were conducted …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"35 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506820","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":"From microbiota to menu: predicting individual responses to dietary components","authors":"Hadar Romano-Zadaka, Nissan Yissachar","doi":"10.1136/gutjnl-2025-334712","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334712","url":null,"abstract":"Over the past few decades, the prevalence of chronic inflammatory and metabolic diseases has risen sharply, coinciding with significant environmental and lifestyle changes. While genetics play a role, the rapid increase suggests that non-genetic factors are key contributors. Among these, the gut microbiota—a vast community of microorganisms residing in the intestines—has emerged as a central regulator of health. A growing body of evidence links microbial imbalances, or dysbiosis, to various diseases, with reduced microbial richness and diversity observed in industrialised populations compared with those in non-industrialised settings. Many beneficial microbial species, once prevalent in the human gut, are now disappearing, likely due to changes in diet, hygiene and antibiotic use. One of the most influential factors shaping the gut microbiota is diet. The Westernised diet, characterised by high consumption of processed foods and food additives, has been associated with microbiota alterations and linked to conditions such as inflammatory bowel disease, obesity and metabolic disorders. Emerging research suggests that some food additives, including emulsifiers1 and artificial sweeteners,2 may exert their harmful effects through microbiota-mediated mechanisms. However, responses to dietary components are highly heterogeneous across individuals, raising an important question: Can we predict individual responses to diet based on microbiota composition and function? Such predictive capabilities could pave the way for personalised nutrition and medicine, tailoring dietary interventions to an individual’s unique microbial makeup. Despite its promise, this approach faces several challenges. Microbiota composition is highly variable across individuals and influenced by numerous factors, including diet, lifestyle, genetics and prior medical treatments. This variability complicates predicting how specific perturbations will affect an individual’s microbiota, as …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"66 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506863","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":"Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis","authors":"Jonel Trebicka, Ferran Aguilar, Alberto Queiroz Farias, Juan-José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto-Vilalta, Patricia Sierra-Casas, Patricia Momoyo Zitelli, Maria Papp, Gustavo Pereira, Paolo Caraceni, Luciana L Goncalves, Carlo Alessandria, Aldo Torre, Wim Laleman, Adrián Gadano, Salvatore Piano, Angelo Z Mattos, Wenyi Gu, Maximilian Joseph Brol, Robert Schierwagen, Frank Erhard Uschner, Julia Fischer, Liliana S C Mendes, Victor Vargas, Mario R Alvares-da-Silva, Raj Mookerjee, Paolo L Bittencourt, Carlos Benitez, Agustín Albillos, Cláudia Couto, Manuel Mendizabal, Rafael Bañares, Claudio L Toledo, Daniel F Mazo, Martin Janicko, Mauricio Castillo-Barradas, Pedro Martin Padilla Machaca, Pietro Gatti, Adelina Zarela-Lozano Miranda, René Malé-Velázquez, Alexander Zipprich, André Castro-Lyra, Thierry Gustot, William Bernal, Alexander L Gerbes, Rajiv Jalan, Javier Fernández, Paolo Angeli, Flair Jose Carrilho, Joan Claria, Richard Moreau, Vicente Arroyo","doi":"10.1136/gutjnl-2024-333876","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333876","url":null,"abstract":"Background and aims Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC. Methods Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients. Results The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission. Conclusions In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506927","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":"Endoscope reprocessing—resource consumption and emissions","authors":"Carlotta Crisciotti, Alessandro Fugazza, Maddalena Menini, Spadaccini Marco, Elena Vanni, Alberto Fumagalli, Paolo Oliva, Tommy Rizkala, Cesare Hassan, Serena Giordano, Rosaria Iacovino, Alessandro Repici","doi":"10.1136/gutjnl-2024-334457","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334457","url":null,"abstract":"Effective reprocessing of reusable GI endoscopes is crucial to minimising patient risks associated with contamination. However, this process poses a considerable environmental challenge. This study aimed to examine the emissions associated with endoscope disinfection, a largely unexplored area. On average, a reprocessing cycle required 57 L water, 65 L air, 1080 watts of electricity and produced 3.30 kgCO2e. These findings highlight the pressing need for sustainable solutions to reduce the environmental impact of endoscope reprocessing while ensuring patient safety remains uncompromised. GI endoscopy represents a significant contributor to greenhouse gas (GHG) emissions and hazardous waste in healthcare.1–3 Several gastroenterology associations have issued guidelines and standards for proper endoscope reprocessing to ensure patient safety and prevent health risks.4 5 Digestive endoscopes are included in the ‘semicritical’ category of items as they contact mucous membranes, thus, the need for high-level disinfection, which, according to the Center for Disease Control (CDC), is defined as the ‘complete elimination of all microorganisms in or on an instrument, except for small numbers of bacterial spores’. This is achieved using high-level disinfectants, peracetic acid being the one used by the unit. However, the impact of this essential process remains largely unknown. Recently, Pioche et al 6 highlighted that—in the life cycle assessment (LCA) of gastroscopes—the decontamination stage of reusable gastroscopes was the greatest contributor to GHG emissions accounting for more than 90% of water consumption and 45% of carbon footprint. The goal of this study is to quantify the environmental burden of reusable endoscope reprocessing, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"51 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506865","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":"Characterisation of MRGPRX2+ mast cells in irritable bowel syndrome","authors":"Lisse Decraecker, María Cuende Estévez, Samuel Van Remoortel, Runze Quan, Nathalie Stakenborg, Zheng Wang, Elisabetta De Marco, Alexandre Denadai-Souza, Maria Francesca Viola, Sonia Garcia Caraballo, Stuart Brierley, Yasuhiro Tsukimi, Gareth Hicks, Wendy Winchester, Jill Wykosky, Andrea Fanjul, Tony Gibson, Mira Wouters, Pieter Vanden Berghe, Hind Hussein, Guy Boeckxstaens","doi":"10.1136/gutjnl-2024-334037","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334037","url":null,"abstract":"Background Mast cell activation is an important driver of abdominal pain in irritable bowel syndrome (IBS). While evidence supports the role of IgE-mediated mast cell activation in visceral pain development in IBS, the role of pseudoallergic MRGPRX2-mediated mast cell activation in this process remains unknown. Objective We investigated whether MRGPRX2-mediated mast cell activation plays a role in abdominal pain development in patients with IBS. Design MRGPRX2 expression in mast cells and other immune cells was characterised across colon layers using flow cytometry. We evaluated whether MRGPRX2 agonists trigger mast cell degranulation and transient receptor potential vanilloid 1 (TRPV1) sensitisation in healthy human colonic submucosal plexus samples using live imaging. Rectal biopsies were then collected from patients with IBS and healthy volunteers (HV) and MRGPRX2+ mast cell frequency, MRGPRX2 expression per cell, mast cell degranulation kinetics in response to MRGPRX2 agonists, MRGPRX2 agonistic activity and presence of MRGPRX2 agonists in biopsy supernatants were assessed. Results MRGPRX2+ mast cells are enriched in the submucosa and muscularis of the healthy human colon. MRGPRX2 agonists induce mast cell degranulation and TRPV1 sensitisation in the healthy colon submucosa. While the frequency of rectal MRGPRX2+ mast cells was unaltered in IBS, submucosal mast cells showed increased degranulation in response to MRGPRX2 agonists in IBS compared with HV. MRGPRX2 agonistic activity was increased in IBS rectal biopsy supernatant compared with HV, which was associated with increased levels of substance P. Conclusion The MRGPRX2 pathway is functionally upregulated in the colon of patients with IBS, supporting its role in abdominal pain in IBS. Data are available upon reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"4 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477599","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":"RNA-based therapies in liver metabolic diseases","authors":"Antonio Fontanellas, Pedro Berraondo, Francesco Urigo, Daniel Jericó, Paolo G V Martini, Fernando Pastor, Matias A Avila","doi":"10.1136/gutjnl-2023-331742","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-331742","url":null,"abstract":"RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA therapies have made significant progress in the treatment of genetic liver diseases, exemplified by small interfering RNA treatments for hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation to improve efficacy and safety. RNA-based gene-editing technologies, such as base editor and prime editor clustered regularly interspaced short palindromic repeats systems, also show promise with their ability to minimise genomic rearrangements and cancer risk. While RNA therapies offer high precision, challenges remain in optimising delivery methods and ensuring long-term safety and efficacy. Lipid nanoparticle-mRNA therapeutics, particularly for protein replacement in rare diseases, have gained support from preclinical successes. Compared with viral gene therapies, mRNA therapies present a safer profile with reduced risks of genomic integration and oncogene activation. However, clinical trials, especially for rare diseases, face limitations such as small sample sizes and short observation periods. Further preclinical studies, including non-human primates, will be essential for refining trial designs. Despite their potential, the high costs of RNA therapies pose a challenge that will require cost–utility models to guide pricing and accessibility. Here, we discuss the fundamental aspects of RNA-based therapeutics and showcase the most relevant preclinical and clinical developments in genetic liver metabolic diseases.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"1 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477472","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":"Multicentre randomised controlled trial of a self-assembling haemostatic gel to prevent delayed bleeding following endoscopic mucosal resection (PURPLE Trial)","authors":"Jan Drews, Markus Zachäus, Tobias Kleemann, Jörg Schirra, Oscar Cahyadi, Oliver Möschler, Christian Schulze, Ingo Steinbrück, Edris Wedi, Oliver Pech, Tobias J Weismüller, Armin Küllmer, Mohamed Abdelhafez, Jochen Wedemeyer, Torsten Beyna, Julian Riedel, Ulrich Paul Halm, Carola Güther, Riccardo Vasapolli, Christian Torres Reyes, Daniel R Quast, Oliver Bachmann, Erini Dedonaki, Jörg Ulrich, Inna Marchuk, Christina Frahm, Tanja Steffen, Peter Wohlmuth, Torsten Bunde, Nele Geßler, Thomas von Hahn","doi":"10.1136/gutjnl-2024-334229","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334229","url":null,"abstract":"Background Prophylactic application of a haemostatic gel to the resection field may be an easy way to prevent delayed bleeding, a frequent complication after endoscopic mucosal resection (EMR). Objective We aimed to evaluate if the prophylactic application of a haemostatic gel to the resection field directly after EMR can reduce the rate of clinically significant delayed bleeding events. Design We conducted a prospective randomised trial of patients undergoing hot-snare EMR of flat lesions in the duodenum (≥10 mm) and colorectum (≥20 mm) at 15 German centres. Prophylactic clip closure was not allowed, but selective clipping or coagulation could be used prior to randomisation to treat intraprocedural bleeding or for prophylactic closure of visible vessels. Patients were randomised to haemostatic gel application or no prophylaxis. The primary endpoint was delayed bleeding within 30 days. Results The trial was stopped early due to futility after an interim analysis. The primary endpoint was analysed in 232 patients (208 colorectal, 26 duodenal). Both groups were comparable in age, sex, comorbidities and lesion characteristics. Preventive measures, such as selective clipping or coagulation, were applied prior to randomisation in 51.9% of cases, with no difference between groups. Delayed bleeding occurred in 14 cases (11.7%; 95% CI 7.1% to 18.6%) after Purastat and in 7 cases (6.3%; 95% CI 3.1% to 12.3%) in the control group (p=0.227), with no difference between colorectal and duodenal subgroups. Conclusion The application of a haemostatic gel following EMR of large flat lesions in the duodenum and colorectum does not reduce the rate of delayed bleeding. Data are available on reasonable request. Data and full trial protocol are available on reasonable request. All data relevant to the study are included in the article of uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"49 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477471","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":"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}