Self-supervised learning for predicting transcriptomic groups on whole slides images in intrahepatic cholangiocarcinoma
Backgrounds & Aims: Transcriptomic classification of intrahepatic cholangiocarcinoma (iCCA) has been recently improved from two classes to five classes, associated with pathological features, targetable genetic alterations and survival. Despite its prognostic and therapeutic value, the classification is not routinely performed due to technical limits such as insufficient material or the cost of molecular analyses. Our aim was to predict iCCA transcriptomic classes on whole-slide digital histological images (WSI) using a self-supervised learning (SSL) model. Methods: Gene expression was investigated using RNA sequencing to class samples in the five transcriptomic classes. We then used a SSL method called GigaSSL. We first trained our model on a discovery set of 769 slides (biopsy and surgical samples, 246 patients) in a 5-fold cross-validation scheme. We then validated the model in a TCGA (n= 29) and a French external validation set (n=32). Results: Our model showed good performance for predicting each transcriptomic class in the discovery set (Area under the curve, AUC: 0.55-0.81), particularly for the Hepatic stem-like class (most frequent group, 37% of cases), with AUC 0.81. The model generalised well for the prediction of four on five of the transcriptomic classes into the two validation sets with AUCs ranging from 0.76 to 0.80 in the TCGA set and from 0.62 to 0.92 in the French external set. Conclusion: We have developed and validated a SSL based model able to predict iCCA transcriptomic classes on routine histological slides (biopsy and surgical samples), which could have an impact on the management of patients. Overall design: populational analysis