Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 39293403.
- Also identified by DOI 10.1016/j.xcrm.2024.101727 and PMC identifier 11525017.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>Interaction</sub> = 0.04). AIMMeR may help reduce pathologist workload and streamline diagnostics in CRC.
Medical subject headings
- Colorectal Neoplasms
- DNA Mismatch Repair
- Microsatellite Instability
- Single-Cell Analysis