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.