RESUMEN
This study addresses the heterogeneity of breast cancer (BC) by employing a Conditional Probabilistic Diffusion Model (CPDM) to synthesize Magnetic Resonance Images (MRIs) based on multi-omic data, including gene expression, copy number variation, and DNA methylation. The lack of paired medical images and genomics data in previous studies presented a challenge, which the CPDM aims to overcome. The well-trained CPDM successfully generated synthetic MRIs for 726 TCGA-BRCA patients, who lacked actual MRIs, using their multi-omic profiles. Evaluation metrics such as Frechet's Inception Distance (FID), Mean Square Error (MSE), and Structural Similarity Index Measure (SSIM) demonstrated the CPDM's effectiveness, with an FID of 2.02, MSE of 0.02, and SSIM of 0.59 based on the 15-fold cross-validation. The synthetic MRIs were used to predict clinical attributes, achieving an Area Under the Receiver-Operating-Characteristic curve (AUROC) of 0.82 and an Area Under the Precision-Recall Curve (AUPRC) of 0.84 for predicting ER+/HER2+ subtypes. Additionally, the MRIs accurately predicted BC patient survival with a Concordance-index (C-index) score of 0.88, outperforming other baseline models. This research demonstrates the potential of CPDMs in generating MRIs based on BC patients' genomic profiles, offering valuable insights for radiogenomic research and advancements in precision medicine. The study provides a novel approach to understanding BC heterogeneity for early detection and personalized treatment.
RESUMEN
BACKGROUND: Breast Cancer (BC) is a highly heterogeneous and complex disease. Personalized treatment options require the integration of multi-omic data and consideration of phenotypic variability. Radiogenomics aims to merge medical images with genomic measurements but encounter challenges due to unpaired data consisting of imaging, genomic, or clinical outcome data. In this study, we propose the utilization of a well-trained conditional generative adversarial network (cGAN) to address the unpaired data issue in radiogenomic analysis of BC. The generated images will then be used to predict the mutations status of key driver genes and BC subtypes. METHODS: We integrated the paired MRI and multi-omic (mRNA gene expression, DNA methylation, and copy number variation) profiles of 61 BC patients from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To facilitate this integration, we employed a Bayesian Tensor Factorization approach to factorize the multi-omic data into 17 latent features. Subsequently, a cGAN model was trained based on the matched side-view patient MRIs and their corresponding latent features to predict MRIs for BC patients who lack MRIs. Model performance was evaluated by calculating the distance between real and generated images using the Fréchet Inception Distance (FID) metric. BC subtype and mutation status of driver genes were obtained from the cBioPortal platform, where 3 genes were selected based on the number of mutated patients. A convolutional neural network (CNN) was constructed and trained using the generated MRIs for mutation status prediction. Receiver operating characteristic area under curve (ROC-AUC) and precision-recall area under curve (PR-AUC) were used to evaluate the performance of the CNN models for mutation status prediction. Precision, recall and F1 score were used to evaluate the performance of the CNN model in subtype classification. RESULTS: The FID of the images from the well-trained cGAN model based on the test set is 1.31. The CNN for TP53, PIK3CA, and CDH1 mutation prediction yielded ROC-AUC values 0.9508, 0.7515, and 0.8136 and PR-AUC are 0.9009, 0.7184, and 0.5007, respectively for the three genes. Multi-class subtype prediction achieved precision, recall and F1 scores of 0.8444, 0.8435 and 0.8336 respectively. The source code and related data implemented the algorithms can be found in the project GitHub at https://github.com/mattthuang/BC_RadiogenomicGAN . CONCLUSION: Our study establishes cGAN as a viable tool for generating synthetic BC MRIs for mutation status prediction and subtype classification to better characterize the heterogeneity of BC in patients. The synthetic images also have the potential to significantly augment existing MRI data and circumvent issues surrounding data sharing and patient privacy for future BC machine learning studies.