Author:
Beaufrère Aurélie,Lazard Tristan,Nicolle Rémy,Lubuela Gwladys,Augustin Jérémy,Albuquerque Miguel,Pichon Baptiste,Pignolet Camille,Priori Victoria,Théou-Anton Nathalie,Lesurtel Mickael,Bouattour Mohamed,Mondet Kévin,Cros Jérôme,Calderaro Julien,Walter Thomas,Paradis Valérie
Abstract
ABSTRACTObjectiveThe transcriptomic classification of intrahepatic cholangiocarcinomas (iCCA) has been recently refined from two to five classes, associated with pathological features, targetable genetic alterations and survival. Despite its prognostic and therapeutic value, the classification is not routinely used in the clinic because of technical limitations, including insufficient tissue material or the cost of molecular analyses. Here, we assessed a self-supervised learning (SSL) model for predicting iCCA transcriptomic classes on whole-slide digital histological images (WSIs)DesignTranscriptomic classes defined from RNAseq data were available for all samples. The SSL method, called Giga-SSL, was used to train our model on a discovery set of 766 biopsy slides (n=137 cases) and surgical samples (n=109 cases) from 246 patients in a five-fold cross-validation scheme. The model was validated in The Cancer Genome Atlas (TCGA) (n= 29) and a French external validation set (n=32).ResultsOur model showed good to very good performance in predicting the four most frequent transcriptomic class in the discovery set (area under the curve [AUC]: 0.63-0.84), especially for the hepatic stem-like class (37% of cases, AUC 0.84). The model performed equally well in predicting these four transcriptomic classes in the two validation sets, with AUCs ranging from 0.76 to 0.80 in the TCGA set and 0.62 to 0.92 in the French external set.ConclusionWe developed and validated an SSL-based model for predicting iCCA transcriptomic classes on routine histological slides of biopsy and surgical samples, which may impact iCCA management by predicting prognosis and guiding the treatment strategy.
Publisher
Cold Spring Harbor Laboratory
Reference36 articles.
1. Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol. 2017;3:1683–91.
2. Intrahepatic cholangiocarcinoma: Molecular markers for diagnosis and prognosis;Surg Oncol,2017
3. Intrahepatic Cholangiocarcinoma
4. Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-analysis;JAMA Surg,2014
5. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma