Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer.
| Autor: | Nowak M; Department of Pathology and Molecular Pathology, Zurich, Zurich, Switzerland., Jabbar F; Cancer Genomics and Immunology Group, The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK., Rodewald AK; Department of Pathology and Molecular Pathology, Zurich, Zurich, Switzerland., Gneo L; Cancer Genomics and Immunology Group, The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK., Tomasevic T; Cancer Genomics and Immunology Group, The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK., Harkin A; CRUK Glasgow Clinical Trials Unit, University of Glasgow, Glasgow, UK., Iveson T; University of Southampton, Southampton, UK., Saunders M; The Christie NHS Foundation Trust, Manchester, UK., Kerr R; Department of Oncology, University of Oxford, Oxford, UK., Oein K; Glasgow Tissue Research Facility, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK., Maka N; Glasgow Tissue Research Facility, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK., Hay J; Glasgow Tissue Research Facility, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK., Edwards J; School of Cancer Sciences, University of Glasgow, Glasgow, UK., Tomlinson I; Department of Oncology, University of Oxford, Oxford, UK., Sansom O; CRUK Beatson Institute of Cancer Research, Garscube Estate, Glasgow, UK., Kelly C; CRUK Glasgow Clinical Trials Unit, University of Glasgow, Glasgow, UK., Pezzella F; Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Kerr D; Nuffield Department of Clinical and Laboratory Sciences, University of Oxford, Oxford, UK., Easton A; Department of Oncology, University of Oxford, Oxford, UK., Domingo E; Department of Oncology, University of Oxford, Oxford, UK., Koelzer VH; Department of Pathology and Molecular Pathology, Zurich, Zurich, Switzerland; Department of Oncology, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland., Church DN; Cancer Genomics and Immunology Group, The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; Oxford NIHR Comprehensive Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: dchurch@well.ox.ac.uk. |
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| Jazyk: | angličtina |
| Zdroj: | Cell reports. Medicine [Cell Rep Med] 2024 Sep 17; Vol. 5 (9), pp. 101727. |
| DOI: | 10.1016/j.xcrm.2024.101727 |
| Abstrakt: | Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples. AIMMeR shows an area under the receiver-operator curve (AUROC) of 0.98, and specificity of ≥75% at 98% sensitivity against pathologist ground truth in stage II/III in two trial cohorts, with positive predictive value of ≥98% for the commonest pattern of somatic MMRd. Lower agreement with microsatellite instability (MSI) testing (AUROC 0.86) reflects discordance between MMR and MSI PCR rather than AIMMeR misclassification. Analysis of the SCOT trial confirms MMRd prognostic value in oxaliplatin-treated patients; while MMRd does not predict differential benefit of chemotherapy duration, it correlates with difference in relapse by regimen (P Competing Interests: Declaration of interests D.N.C. has participated in advisory boards for MSD and has received research funding on behalf of the TransSCOT consortium from HalioDx for analyses independent of this study. V.H.K. has served as an invited speaker on behalf of Indica Labs, SPCC, and Takeda and has received project-based research funding from The Image Analysis Group and Roche outside of the submitted work. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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