Integration of histopathological images and multi-dimensional omics analyses predicts molecular features and prognosis in high-grade serous ovarian cancer

Abstract

Objective: This study used histopathological image features to predict molecular features, and combined with multi-dimensional omics data to predict overall survival (OS) in high-grade serous ovarian cancer (HGSOC).

Methods: Patients from The Cancer Genome Atlas (TCGA) were distributed into training set (n = 115) and test set (n = 114). In addition, we collected tissue microarrays of 92 patients as an external validation set. Quantitative features were extracted from histopathological images using CellProfiler, and utilized to establish prediction models by machine learning methods in training set. The prediction performance was assessed in test set and validation set.

Results: The prediction models were able to identify BRCA1 mutation (AUC = 0.952), BRCA2 mutation (AUC = 0.912), microsatellite instability-high (AUC = 0.919), microsatellite stable (AUC = 0.924), and molecular subtypes: proliferative (AUC = 0.961), differentiated (AUC = 0.952), immunoreactive (AUC = 0.941), mesenchymal (AUC = 0.918) in test set. The prognostic model based on histopathological image features could predict OS in test set (5-year AUC = 0.825) and validation set (5-year AUC = 0.703). We next explored the integrative prognostic models of image features, genomics, transcriptomics and proteomics. In test set, the models combining two omics had higher prediction accuracy, such as image features and genomics (5-year AUC = 0.834). The multi-omics model including all features showed the best prediction performance (5-year AUC = 0.911). According to risk score of multi-omics model, the high-risk and low-risk groups had significant survival differences (HR = 18.23, p < 0.001).

Conclusions: These results indicated the potential ability of histopathological image features to predict above molecular features and survival risk of HGSOC patients. The integration of image features and multi-omics data may improve prognosis prediction in HGSOC patients.

Keywords: Genomics; Histopathology; Ovarian cancer; Proteomics; Transcriptomics.