Machine Learning–Based Pathomics Model Predicts Angiopoietin-2 Expression and Prognosis in Hepatocellular Carcinoma

Angiopoietin-2 (ANGPT2) shows promise as prognostic marker and therapeutic target in hepatocellular carcinoma (HCC). However, assessing ANGPT2 expression and prognostic potential using histopathology images viewed with naked eye is challenging. Herein, machine learning was employed to develop a pathomics model for analyzing histopathology images to predict ANGPT2 status. HCC cases obtained from The Cancer Genome Atlas (TCGA-HCC; n = 267) were randomly assigned to the training or testing set, and cases from a single center were employed as a validation set (n = 91). In the TCGA-HCC cohort, the group with high ANGPT2 expression had a significantly lower overall survival compared with the group with low ANGPT2. Histopathologic features in the training set were extracted, screened, and incorporated into a gradient-boosting machine model that generated a pathomics score, which successfully predicted ANGPT2 expression in the three data sets and showed remarkable risk stratification for overall survival in both the TCGA-HCC (P < 0.0001) and single-center cohorts (P = 0.001). Multivariate analysis suggested that the pathomics score could serve as a predictor of prognosis (P < 0.001). Bioinformatics analysis illustrated a distinction in tumor growth and development related gene-enriched pathways, vascular endothelial growth factor-related gene expression, and immune cell infiltration between high and low pathomics scores. This study indicates that the use of histopathology image features can enhance the prediction of molecular status and prognosis in HCC. The integration of image features with machine learning may improve prognosis prediction in HCC.