Yesung Cho, Dongmyung Shin, Sujeong Hong, Jooyeon Lee, Seongmin Park, Geongyu Lee, Won Young Park, Bongjin Park 等 10 位作者
Prostate cancer is among the most frequently diagnosed malignancies in men worldwide. However, precise prediction of biochemical recurrence (BCR) after radical prostatectomy remains challenging. Here, we propose a computationally efficient multi section whole slide image analysis framework designed to capture the whole gland tumor landscape. We curated a large scale dataset comprising 23,451 slides from 789 patients and systematically optimized patch and slide sub sampling to substantially reduce the computational cost of training and inference. Under this efficient configuration, the framework achieved strong predictive performance for 1- and 2-year BCR, with discrimination and clinical net benefit comparable to or exceeding those of established clinical benchmarks. In multivariable Cox proportional hazards analysis, the AI derived risk score remained an independent prognostic factor among the covariates examined, and its integration with clinical variables further improved prognostic performance. External validation in an independent cohort provided preliminary evidence of transferability. Finally, attention-dispersion analysis showed that the model drew prognostic information from multiple sections, consistent with the multifocal nature of prostate cancer. Collectively, these findings support the potential of multi section slide analysis as a scalable approach for postoperative BCR risk assessment in prostate cancer.
Yesung Cho, Ji Hwan Park, Chan Il Kim, Hyewon Kim, Honglan Li, Yumin Lee, Geongyu Lee, Sujeong Hong 等 31 位作者
Outcome informed AI can localize prognostically relevant regions in digital pathology, but directly characterizing the molecular basis of these spatial predictions remains challenging. Here, we developed an outcome informed, AI-guided deep visual proteomics framework that uses recurrence-risk heatmaps to guide physical tissue sampling and mass spectrometry-based spatial proteomics in triple-negative breast cancer (TNBC). In 156 patients, high- and low-risk regions coexisted within the tumor compartment and showed distinct nuclear and architectural features, indicating intratumoral variation beyond broad tissue identity. Guided by these maps, we physically isolated and profiled 46 AI-defined high- and low-risk tumor regions from two recurrent cases. High-risk regions were enriched for mitotic programs, whereas low-risk regions showed immune- and antigen-presentation-associated programs. We used proteins that consistently differed between high- and low-risk regions to construct a 13-protein composite. The composite showed a significant effect to discriminate highly recurrent patients from less recurrent patients in an expanded TNBC cohort, while the corresponding transcript-based score showed a similar trend in METABRIC. Integrating the protein composite with the H&E-derived risk score improved out-of-bag discrimination, increasing the C-index from 0.679 to 0.739 and the 5-year time-dependent AUC from 0.675 to 0.770. These findings establish outcome-informed H&E risk maps as spatial guides for molecular discovery, extending prognostic AI from prediction toward direct biological interrogation of recurrence-associated tissue states.