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- 조회96
박선호Sunho Park
Vanderbilt University Medical Center
npj Digit. Med., May 19 2025, 8 (1) | https://doi.org/10.1038/s41746-025-01580-8
Deep Gaussian process with uncertainty estimation for microsatellite instability and immunotherapy response prediction from histology
Sunho Park1,16, Morgan F. Pettigrew2,16, Yoon Jin Cha3,16, In-Ho Kim4,16, Minji Kim1, Imon Banerjee5, Isabel Barnfather6, Jean R. Clemenceau1, Inyeop Jang1, Hyunki Kim7, Younghoon Kim8, Rish K. Pai9, Jeong Hwan Park10, N. Jewel Samadder11, Kyo Young Song12, Ji-Youn Sung13, Jae-Ho Cheong14, Jeonghyun Kang15, Sung Hak Lee8, Sam C. Wang2 & Tae Hyun Hwang1
1Vanderbilt University Medical Center, Nashville, TN, USA.
2Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
4Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
5Department of Radiology, Mayo Clinic, Phoenix, AZ, USA.
6Department of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.
7Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
8Department of Hospital Pathology,Seoul St.Mary’s Hospital, College ofMedicine, The Catholic University ofKorea, Seoul, Korea.
9Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA.
10Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
11Department of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA.
12Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College ofMedicine, The Catholic University of Korea, Seoul, Korea.
13Department of Pathology, College of Medicine, Kyung Hee University hospital, Kyung Hee University, Seoul, Korea.
14Department of Surgery, Department of Biochemistry and Molecular Biology, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea.
15Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
16These authors contributed equally: Sunho Park, Morgan F. Pettigrew, Yoon Jin Cha, In-Ho Kim.
Corresponding authors
Correspondence to Jae-Ho Cheong, Jeonghyun Kang, Sung Hak Lee, Sam C. Wang or Tae Hyun Hwang.
1Vanderbilt University Medical Center, Nashville, TN, USA.
2Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
4Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
5Department of Radiology, Mayo Clinic, Phoenix, AZ, USA.
6Department of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA.
7Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
8Department of Hospital Pathology,Seoul St.Mary’s Hospital, College ofMedicine, The Catholic University ofKorea, Seoul, Korea.
9Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA.
10Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
11Department of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA.
12Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College ofMedicine, The Catholic University of Korea, Seoul, Korea.
13Department of Pathology, College of Medicine, Kyung Hee University hospital, Kyung Hee University, Seoul, Korea.
14Department of Surgery, Department of Biochemistry and Molecular Biology, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea.
15Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
16These authors contributed equally: Sunho Park, Morgan F. Pettigrew, Yoon Jin Cha, In-Ho Kim.
Corresponding authors
Correspondence to Jae-Ho Cheong, Jeonghyun Kang, Sung Hak Lee, Sam C. Wang or Tae Hyun Hwang.
Abstract
Determining tumor microsatellite status has significant clinical value because tumors that are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) respond well to immune checkpoint inhibitors (ICIs) and oftentimes not to chemotherapeutics. We propose MSI-SEER, a deep Gaussian process-based Bayesian model that analyzes H&E whole-slide images in weakly-supervised-learning to predict microsatellite status in gastric and colorectal cancers. We performed extensive validation using multiple large datasets comprised of patients from diverse racial backgrounds. MSI-SEER achieved state-of-the-art performance with MSI prediction by integrating uncertainty prediction. We achieved high accuracy for predicting ICI responsiveness by combining tumor MSI status with stroma-to-tumor ratio. Finally, MSI-SEER's tile-level predictions revealed novel insights into the role of spatial distribution of MSI-H regions in the tumor microenvironment and ICI response.
논문정보
- Research article
- 2025년 05월 (BRIC 등록일 2025-05-20)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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