Multiple instance learning-based prediction of programmed death-ligand 1 (PD-L1) expression from hematoxylin and eosin (H&E)-stained histopathological images in breast cancer.

Journal: PeerJ
PMID:

Abstract

Programmed death-ligand 1 (PD-L1) is an important biomarker increasingly used as a predictive marker in breast cancer immunotherapy. Immunohistochemical quantification remains the standard method for assessment. However, it presents challenges related to time, cost, and reliability. Hematoxylin and eosin (H&E) staining is a routine method in cancer pathology, known for its accessibility and consistently reliability. Deep learning has shown the potential in predicting biomarkers in cancer histopathology. This study employs a weakly supervised multiple instance learning (MIL) approach to predict PD-L1 expression from H&E-stained images using deep learning techniques. In the internal test set, the TransMIL method achieved an area under the curve (AUC) of 0.833, and in an independent external test set, it achieved an AUC of 0.799. Additionally, since RNA sequencing results indicate a threshold that allows for the separation of H&E pathology images, we further validated our approach using the public TCGA-TNBC dataset, achieving an AUC of 0.721. These findings demonstrates that the Transformer-based TransMIL model can effectively capture highly heterogeneous features within the MIL framework, exhibiting strong cross-center generalization capabilities. Our study highlights that appropriate deep learning techniques can enable effective PD-L1 prediction even with limited data, and across diverse regions and centers. This not only underscores the significant potential of deep learning in pathological artificial intelligence (AI) but also provides valuable insights for the rational and efficient allocation of medical resources.

Authors

  • Zhen Da
    Department of Pathology, People's Hospital of Xizang Autonomous Region, Lhasa, Xizang, China.
  • Heng Yang
    State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
  • Bianba Zhaxi
    Department of General Surgery, People's Hospital of Xizang Autonomous Region, Lhasa, Xizang, China.
  • Kaixiang Sun
    School of Electrical and Electronic Engineering, Chongqing University of Technology, Chongqing, China.
  • Guohui Bai
    Department of General Surgery, People's Hospital of Xizang Autonomous Region, Lhasa, Xizang, China.
  • Chao Wang
    College of Agriculture, Shanxi Agricultural University, Taigu, Shanxi, China.
  • Feiyan Wang
    Kunyuan Fangqing Medical Technology Co., LTD, Guangzhou, Guangdong, China.
  • Weijun Pan
    State Key Laboratory of Severe Weather & Key Laboratory of Atmospheric Chemistry of CMA, Chinese Academy of Meteorological Sciences, Beijing 100081, China.
  • Rui Du
    Department of Obstetrics and Gynecology, Xinhua Hospital Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.