Loading...
Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer
Nowak, M. Jabbar, F. Rodewald, A. K. Gneo, L. Tomasevic, T. Harkin, A. Iveson, T. Saunders, Mark Kerr, R. Oein, K.
Nowak, M.
Jabbar, F.
Rodewald, A. K.
Gneo, L.
Tomasevic, T.
Harkin, A.
Iveson, T.
Saunders, Mark
Kerr, R.
Oein, K.
Citations
Altmetric:
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.
Description
Date
2024
Publisher
Collections
Files
Keywords
Type
Article
Citation
Nowak M, Jabbar F, Rodewald AK, Gneo L, Tomasevic T, Harkin A, et al. Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer. Cell reports Medicine. 2024 Sep 17;5(9):101727. PubMed PMID: 39293403. Pubmed Central PMCID: PMC11525017. Epub 2024/09/19. eng.