Gastroenterology

BACKGROUND & AIMS: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiological studies that although most colorectal cancers originate from adenomas, only a small fraction of adenomas (3-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. METHODS: We profiled by mass spectrometry (MS)-based proteomics combined with machine learning analysis a selected cohort of formalin fixed paraffin embedded HG adenomas with long clinical follow-up, collected as part of the Danish national screening program...

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BACKGROUND: Excess copper causes hepatocyte death in hereditary Wilson disease (WD). Current WD treatments by copper-binding chelators may gradually reduce copper overload; they fail, however, to bring hepatic copper close to normal physiological levels. Consequently, lifelong daily dose regimens are required to hinder disease progression. This may result in severe issues due to non-adherence or unwanted drug reactions, but also in drug switching and ultimate treatment failures. STUDY AIMS: To comparatively test bacteria-derived copper binding agents - methanobactins (MBs) - for efficient liver copper depletion in WD rats, as well as their safety and effect duration...

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BACKGROUND AND AIMS: Colorectal cancer (CRC) screening guidelines include screening-colonoscopy and sequential high sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening-colonoscopy compared to sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening-colonoscopy versus sequential and non-sequential HSgFOBT...

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BACKGROUND & AIMS: Dysbiosis of gut microbiota is linked to the development of colorectal cancer (CRC). However, microbiota-based stratification of CRC tissue and how this relates to clinico-molecular characteristics and prognosis remains to be clarified. METHODS: Tumour and normal mucosa from 423 stage I-IV patients were profiled by bacterial 16S rRNA gene sequencing. Tumours were characterised for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), APC, BRAF, KRAS, PIK3CA, FBXW7, SMAD4 and TP53 mutations; subsets for chromosome instability (CIN), mutation signatures and consensus molecular subtypes (CMS)...

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BACKGROUND AND AIMS: Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes. METHODS: We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (i) immune-targeted single-cell RNA sequencing (scRNA-seq, n = 20 patients) and (ii) protein expression profiling by a targeted antibody panel for mass cytometry (CyTOF, n = 12 patients)...

BACKGROUND AND AIMS: Colorectal cancer (CRC) is one of the most prevalent tumours worldwide, with incidences (particularly in the context of early-onset cases) quickly increasing despite important prevention efforts, mainly in the form of population-wide screening programmes. Although many cases present a clear familial component, the current list of hereditary CRC genes still leaves a considerable proportion of the cases unexplained. METHODS: In this work, we utilised whole-exome sequencing approaches on 19 unrelated patients with unexplained colonic polyposis to identify candidate CRC predisposition genes...

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