4.8 Article

Predicting Molecular Phenotypes from Histopathology Images: A Transcriptome-Wide Expression-Morphology Analysis in Breast Cancer

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CANCER RESEARCH
卷 81, 期 19, 页码 5115-5126

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AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-21-0482

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  1. Swedish Research Council [ERAPERMED2019-224-ABCAP]
  2. Swedish Cancer Society
  3. Karolinska Institutet
  4. MedTechLabs
  5. Swedish escience Research Centre (SeRC)-eCPC
  6. Stockholm Region
  7. Stockholm Cancer Society
  8. Swedish Breast Cancer Association
  9. Academy of Finland [326463, 341967, 335976, 312043]
  10. Cancer Foundation Finland
  11. ERA PerMed ABCAP
  12. CSC-IT Center for Science (Finland) [2001568]
  13. Tampere University graduate school
  14. University of Turku Graduate School UTUGS
  15. Turku University Foundation
  16. Swedish Society for Medical Research (Svenska Sallskapet for Medicinsk Forsknings-SSMF)
  17. Academy of Finland (AKA) [335976] Funding Source: Academy of Finland (AKA)

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The study demonstrated that deep learning analysis of transcriptome-wide expression morphology enables the prediction of mRNA expression and proliferation markers from routine histopathology whole slide images in breast cancer. This approach represents a significant advancement in predicting tumor molecular characteristics.
Molecular profiling is central in cancer precision medicine but remains costly and is based on tumor average profiles. Morphologic patterns observable in histopathology sections from tumors are determined by the underlying molecular phenotype and therefore have the potential to be exploited for prediction of molecular phenotypes. We report here the first transcriptome-wide expression-morphology (EMO) analysis in breast cancer, where individual deep convolutional neural networks were optimized and validated for prediction of mRNA expression in 17,695 genes from hematoxylin and eosin-stained whole slide images. Predicted expressions in 9,334 (52.75%) genes were significantly associated with RNA sequencing estimates. We also demonstrated successful prediction of an mRNA-based proliferation score with established clinical value. The results were validated in independent internal and external test datasets. Predicted spatial intratumor variabilities in expression were validated through spatial transcriptomics profiling. These results suggest that EMO provides a cost-efficient and scalable approach to predict both tumor average and intratumor spatial expression from histopathology images. Significance: Transcriptome-wide expression morphology deep learning analysis enables prediction of mRNA expression and proliferation markers from routine histopathology whole slide images in breast cancer.

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