Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2024-09-17 DOI:10.1016/j.xcrm.2024.101727

Marta Nowak, Faiz Jabbar, Ann-Katrin Rodewald, Luciana Gneo, Tijana Tomasevic, Andrea Harkin, Tim Iveson, Mark Saunders, Rachel Kerr, Karin Oein, Noori Maka, Jennifer Hay, Joanne Edwards, Ian Tomlinson, Owen Sansom, Caroline Kelly, Francesco Pezzella, David Kerr, Alistair Easton, Enric Domingo, David N. Church

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引用次数: 0

Abstract

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_Interaction = 0.04). AIMMeR may help reduce pathologist workload and streamline diagnostics in CRC.

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基于单细胞人工智能的结直肠癌 DNA 错配修复缺陷检测及其预后和预测价值

建议对所有结直肠癌（CRC）进行 DNA 错配修复缺陷（MMRd）检测。将这一检测自动化可实现精准医疗，尤其是在提供深度学习（DL）方法无法捕捉的病因学信息时。我们介绍的 AIMMeR 是一种基于人工智能的方法，用于确定常规病理样本中单细胞水平的错配修复（MMR）蛋白表达。在两个试验队列中，AIMMeR 的接收者操作者曲线下面积（AUROC）为 0.98，与病理学家地面实况相比，特异性≥75%，灵敏度为 98%，对最常见的体细胞 MMRd 模式的阳性预测值≥98%。与微卫星不稳定性（MSI）检测的一致性较低（AUROC 0.86），反映了MMR和MSI PCR之间的不一致，而不是AIMMeR的错误分类。对SCOT试验的分析证实了MMRd在奥沙利铂治疗患者中的预后价值；虽然MMRd不能预测化疗持续时间的不同获益，但它与不同方案的复发差异相关（PInteraction = 0.04）。AIMMeR 可能有助于减轻病理学家的工作量，简化对 CRC 的诊断。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.