Gut最新文献

{"title":"Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study","authors":"Ze-Rong Cai, Yong-Qiang Zheng, Yan Hu, Meng-Yao Ma, Yi-Jin Wu, Jia Liu, Lu-Ping Yang, Jia-Bo Zheng, Tian Tian, Pei-Shan Hu, Ze-Xian Liu, Lin Zhang, Rui-Hua Xu, Huai-Qiang Ju","doi":"10.1136/gutjnl-2024-333522","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333522","url":null,"abstract":"Background and objective Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis. Designs Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves. Results RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effectively identify GC patients with negative gastrointestinal tumour biomarkers and those in early-stage. Furthermore, molecular biological assays revealed that knockdown of DGCR9 inhibited GC tumour growth. Conclusions Our proposed serum exosome ncRNA feature provides a promising liquid biopsy approach for enhancing the early diagnosis of GC. Data are available in a public, open access repository. The raw sequence data generated in the screening phase have been deposited in the Genome Sequence Archive (GSA-Human: HRA008261) that are publicly accessible at <https://ngdc.cncb.ac.cn/gsa-human>.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"72 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925002","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":"Aspirin is associated with lower risk of pancreatic cancer and cancer-related mortality in patients with diabetes mellitus","authors":"Jing Tong Tan, Xianhua Mao, Ho-Ming Cheng, Wai-Kay Seto, Wai-K Leung, Ka-Shing Cheung","doi":"10.1136/gutjnl-2024-333329","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333329","url":null,"abstract":"Background Patients with type 2 diabetes mellitus (T2DM) have higher pancreatic cancer (PC) risk. While aspirin has chemopreventive effects on digestive cancers, its effect on PC among patients with T2DM is unclear. Methods This retrospective cohort study identified newly diagnosed adult patients with T2DM in Hong Kong between 2001 and 2015 from a territory-wide healthcare registry. Exclusion criteria were history of PC, pancreatic cyst, IgG4 disease, or pancreatectomy. To address reverse causality between PC and T2DM, we excluded patients with PC diagnosed within 1 year of T2DM. We also excluded patients with less than 1 year of observation. Primary outcome was PC, and secondary outcomes were PC-related and all-cause mortality. Aspirin use was treated as time-varying variable (≥180 day-use/year) to address immortal-time bias, and multivariable Cox regression model was employed to derive adjusted HR (aHR). Propensity-score (PS) matching was used as secondary analysis. Results Among 343 966 newly diagnosed patients with T2DM (median follow-up: 10.5 years; IQR: 7.7–14.5 years), 1224 (0.36%) developed PC. There were 51 151 (14.9%) deaths from any cause, and 787 (0.2%) died from PC. Aspirin use was associated with lower PC risk in both time-dependent (aHR: 0.58; 95% CI 0.49 to 0.69) and PS matching analysis (aHR: 0.61; 95% CI 0.48 to 0.77). An inverse relationship was observed with increasing dose and duration of aspirin use ( P trend<0.001). Aspirin was also associated with a lower risk of PC-related mortality (aHR: 0.43; 95% CI 0.34 to 0.53) and all-cause mortality (aHR: 0.78; 95% CI 0.76 to 0.80). Conclusion Aspirin use may be an oncopreventive strategy to reduce PC risk in patients with T2DM. Further studies are warranted to validate the study findings. Data may be obtained from a third party and are not publicly available. The data of this study were provided by the Hong Kong Hospital Authority. Restrictions apply to the availability of these data, which were used under license.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"20 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917125","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":"Correction: The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells","authors":"BMJ Publishing Group Ltd and British Society of Gastroenterology","doi":"10.1136/gutjnl-2023-330995corr1","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-330995corr1","url":null,"abstract":"López-Gil JC, García-Silva S, Ruiz-Cañas L, et al. The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"28 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797047","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":"Colonic motility investigation by modern techniques: time to ‘reclaim’ the value of physiology?","authors":"Gabrio Bassotti","doi":"10.1136/gutjnl-2024-334537","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334537","url":null,"abstract":"I read with interest the recent article of Wilkinson-Smith and colleagues on the assessment of colonic motility by means of MRI and high-resolution colonic manometry (HRCM),1 showing that patients with constipation and irritable bowel syndrome (IBS) may display some abnormalities when such investigated. I would like to make some observations on this study. Since HRCM probes were positioned 35 cm from the anal verge, I would be very cautious in claiming that those were ‘colonic’ studies, since (by considering the physiological bending of the large bowel) at the very best only a very limited colonic area was studied. Indeed, the authors in the methods reported that only the sigmoid colon was actually investigated in a systematic …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"134 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908218","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":"SPHINX, a Guardian of Wisdom","authors":"Anke Onnekink, Roy L J van Wanrooij, Jeanin E Van Hooft","doi":"10.1136/gutjnl-2024-334569","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334569","url":null,"abstract":"We thank Ramchandani et al for their letter on the SPHINX trial and appreciate the opportunity to address their points.1 2 The SPHINX trial aimed to assess whether endoscopic sphincterotomy (ES) could reduce post-ERCP pancreatitis (PEP). However, quantifying this effect proved difficult due to conflicting results from previous, heterogeneous randomised controlled trials (RCTs), which differed in sample size, patient populations and stent types.3–5 The trial by Zhou et al (2012) reported a 69% relative risk reduction in PEP after ES, which served as reference for our sample size calculation.3 However, since the other trials did not show this benefit, we considered this effect overestimated.4 5 The SPHINX trial was designed to detect a 50% relative risk reduction in PEP in patients with suspected distal malignant biliary obstruction (MBO). Based on data from a Dutch prospective …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"242 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908217","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":"Accuracy of histopathology evaluation in diminutive colonic polyps diagnosed as neoplastic by computer-aided characterisation","authors":"Roupen Djinbachian, Heiko Pohl, Douglas K Rex, Alan Barkun, Cesare Hassan, Geneviève Soucy, Bich N Nguyen, Daniel von Renteln","doi":"10.1136/gutjnl-2024-332943","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332943","url":null,"abstract":"The removal of colorectal polyps followed by histological evaluation is the current standard of care. Intracolonoscopy computer-aided characterisation (computer-assisted diagnosis (CADx)) has emerged as an alternative strategy to possibly avoid histopathology after removal. However, each of these approaches can be limited by cases in which a diagnosis is not possible or inaccurate. We conducted a post hoc analysis of a prospective clinical study involving 249 diminutive polyps diagnosed by CADx in 164 consecutive patients. Of those polyps, 29 were diagnosed as ‘normal mucosa’ on histopathology (11.6%). Polyps diagnosed as ‘normal mucosa’ were reviewed by two independent blinded pathologists, and 24.1% were reassessed as adenomas after additional sections were performed. Besides superficial sectioning (24.1%), fragmentation (44.8%) and inadequate specimen preparation and handling (31.0%) were considered as reasons for misdiagnosis. Reassessment decreased the overall accuracy of histopathology to 88.4% (95% CI 83.7% to 92.1%). On the other hand, in these 29 cases, CADx diagnosed all polyps as neoplastic, accounting for an overall accuracy of 85.5% (95% CI 80.2% to 89.8%). Therefore, a combined approach may allow for improved diagnostic accuracy. The current standard of care for colorectal polyps involves analysis in a pathology laboratory. However, this process includes several steps including resection and retrieval, during which specimens may fracture or be lost, as well as processing, embedding, sectioning and final analysis, all of which can introduce errors and misdiagnoses. Recent publications have indicated that the final pathology report can indeed be incorrect after polyp resection, with cases discordant with optical diagnosis undergoing a series of additional reviews, which continued until concordance was achieved.1 This approach …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"48 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908199","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":"Trends and cross-country inequality in the incidence of GI cancers among the working-age population from 1990 to 2021: a Global Burden of Disease 2021 analysis","authors":"Yiming Song, Xiaoyi Wang, Yufeng Shen, Liping Chen, Liuyi Yang, Ruilan Wang, Junyu Lu, Zhifang Gao, Xiaolu Lin, Yan Song, Qingwei Zhang, Xiaobo Li","doi":"10.1136/gutjnl-2024-333932","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333932","url":null,"abstract":"Background GI cancers pose an increasing global health burden, with their impact on the working-age population (WAP) aged 15–64 years remaining largely unexplored despite the crucial role of this group in societal and economic well-being. Objective To assess trends and cross-country inequality in the global burden of six GI cancers from 1990 to 2021 among individuals in the WAP. Design The 2021 Global Burden of Disease study dataset was used to obtain estimates of GI cancer incidence and 95% uncertainty intervals, including the number of cases, crude incidence rate and age-standardised incidence rate (ASIR). WAP GI cancer epidemiology was assessed at the national, regional and global levels, evaluating trends from 1990 to 2021 from overall, local and Sociodemographic Index (SDI) perspectives and using standard health equity methods to quantify cross-country inequality. Results Colorectal cancer exhibited the greatest burden of GI cancer among the WAP in 2021. From 1990 to 2021, the number of GI cancer cases rose by 51.9%, although the ASIR declined by 23.4%. These rates exhibit geographic variation, with the most cases and the highest ASIR in China and Mongolia, respectively. Incidence was disproportionately concentrated in higher SDI countries, and worsening inequality was evident over time. Conclusions While the ASIR of GI cancer is trending downwards among the WAP, high incidence rates, regional variability and an unequal burden of disease emphasise the need for flexible, targeted medical interventions to support policymaking and medical resource allocation. Data are available in a public, open access repository. Data are available in a public, open access repository. Data from the Global Burden of Disease (GBD) study in 2021 can be accessed using the GBD Results Tool (<https://vizhub.healthdata.org/gbd-results/>) which the Institute for Health Metrics and Evaluation maintains. The GBD data do not require licensing for non-commercial use.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"25 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908216","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":"Frequency of de novo PRSS1 pathogenic variants in a French cohort of idiopathic pancreatitis","authors":"Emmanuelle Masson, Anne-Laure Vedie, Frédérique Maire, Tiphaine Godet, Louis Buscail, Vinciane Rebours, Claude Férec, Jian-Min Chen","doi":"10.1136/gutjnl-2024-333908","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333908","url":null,"abstract":"We read with great interest the recent publication by Lou et al ,1 which addressed the challenge of false positives in next-generation sequencing (NGS) due to highly homologous PRSS1 paralogs.2 3 PRSS1 was the first gene linked to chronic pancreatitis,4 with p.Arg122His (c.365G>A) and p.Asn29Ile (c.86A>T) being the most common mutations associated with the Mendelian form of the disease. Accurate identification of PRSS1 variants is crucial for genetic diagnosis and counselling, guiding both patient management and familial risk assessment. Although PRSS1 pathogenic variants are typically inherited in an autosomal dominant manner, they have also been reported in idiopathic pancreatitis, defined by the absence of precipitating factors and a negative family history prior to genetic analysis.5–8 However, large-scale data on the frequency of de novo PRSS1 variants in idiopathic pancreatitis remain limited. To address this gap, we analysed data from a large French cohort. From 1996 to July 2024, we genetically analysed 6872 patients with idiopathic pancreatitis, including both acute and chronic forms. Of these, 82 patients (1.2%) were identified to carry a PRSS1 pathogenic variant, with classifications based on the expert perspective of the Franco-Chinese GREPAN study group.9 …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"26 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908226","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":"Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma","authors":"Ekaterina Zhuravleva, Monika Lewinska, Colm J O'Rourke, Antonio Pea, Asif Rashid, Ann W Hsing, Andrzej Taranta, David Chang, Yu-Tang Gao, Jill Koshiol, Rui Caetano Oliveira, Jesper B Andersen","doi":"10.1136/gutjnl-2024-333368","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333368","url":null,"abstract":"Background and objective Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. We applied an approach of integrative genomics characterising patients with AMPAC exploring molecular subtypes that may guide personalised treatments. Design We analysed the mutational landscapes of 170 patients with AMPAC. The discovery included 110 tumour/normal pairs and the validation comprised 60 patients. In a tumour subset, we interrogated the transcriptomes and DNA methylomes. Patients were stratified based on mutational signatures and associated with molecular and clinical features. To evaluate tumour and immune cellularity, 22 tumours were independently assessed histomorphologically and by digital pathology. Results We defined three patient clusters by mutational signatures independent of histomorphology. Cluster 1 (C1) was defined by spontaneous deamination of DNA 5-methylcytosine and defective mismatch repair. C2 and C3 were related to the activity of transcription-coupled nucleotide excision repair but C3 was further defined by the polymerase eta mutational process. C1–2 showed enrichment of Wnt pathway alterations, aberrant DNA methylation profiles, immune cell exclusion and patients with poor prognosis. These features were associated with a hypermutator phenotype caused by C>T alterations at CpGs. C3 patients with improved overall survival were associated with activation of immune-related pathways, immune infiltration and elevated expression of immunoinhibitory checkpoint genes. Conclusion Immunogenicity and Wnt pathway associations, emphasised by the mutational signatures, defined patients with prospective sensitivity to either immunotherapy or Wnt pathway inhibitors. This emphasises a novel mutational signature-based AMPAC classification with prognostic potential, suggesting prospective implications for subgroup-specific management of patients with AMPAC. Data are available in a public, open access repository. Data sets relevant to this study are included in the supplementary information and available at GEO with accession number GSE159099.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"14 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887670","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":"Much ado about EoE","authors":"David A Katzka","doi":"10.1136/gutjnl-2024-334394","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334394","url":null,"abstract":"In 1996, a landmark study from Kelly et al demonstrated that placement of children with oesophageal eosinophilia on an elemental diet, that is, a diet devoid of all food antigens, led to histological and symptomatic normalisation.1 Over the past three decades, this simple understanding of eosinophilic oesophagitis (EoE) has evolved from a one-act play to a highly complex drama involving multiple scenes and actors. Recently in Gut, Santacroce et al 2 carefully and elegantly illustrated an understandable and exciting view of the pathogenesis of EoE. Roughly, three acts were presented to advance the pathobiology of EoE: barrier dysfunction, inflammation and tissue remodelling. The observation that large protein antigens and pathogens can penetrate the oesophageal epithelium is a novel concept.3 Dysfunction of this barrier leading to antigen penetration is manifest pathologically by dilation of intracellular spaces, physiologically by methods that demonstrate increased permeability and mechanistically by disruption of cell–cell adhesion proteins such as tight junctions and desmosomes. The initiating events for this perturbation are unclear but they range from localised epithelial microbial effects on tight junctions to mucosal damage from environmental toxins and a hyperproliferative response of the epithelial basal zone. Specific gene variations such …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"11 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886912","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}