Artificial intelligence model predicts M2 macrophage levels and HCC prognosis with only globally labeled pathological images

Background and aims The levels of M2 macrophages are significantly associated with the prognosis of hepatocellular carcinoma (HCC), however, current detection methods in clinical settings remain challenging. Our study aims to develop a weakly supervised artificial intelligence model using globally labeled histological images, to predict M2 macrophage levels and forecast the prognosis of HCC patients by integrating clinical features. Methods CIBERSORTx was used to calculate M2 macrophage abundance. We developed a slide-level, weakly-supervised clustering method for Whole Slide Images (WSIs) by integrating Masked Autoencoders (MAE) with ResNet-32t to predict M2 macrophage abundance. Results We developed an MAE-ResNet model to predict M2 macrophage levels using WSIs. In the testing dataset, the area under the curve (AUC) (95% CI) was 0.73 (0.59-0.87). We constructed a Cox regression model showing that the predicted probabilities of M2 macrophage abundance were negatively associated with the prognosis of HCC (HR=1.89, p=0.031). Furthermore, we incorporated clinical data, screened variables using Lasso regression, and built the comprehensive prediction model that better predicted prognosis. (HR=2.359, p=0.001). Conclusion Our models effectively predicted M2 macrophage levels and HCC prognosis. The findings suggest that our models offer a novel method for determining biomarker levels and forecasting prognosis, eliminating additional clinical tests, thereby delivering substantial clinical benefits.