Relationship between EZH2 expression and prognosis of patients with hepatocellular carcinoma using a pathomics predictive model.

Background: Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is overexpressed in hepatocellular carcinoma, promoting tumorigenesis and correlating with poor prognosis. Traditional histopathological examinations are insufficient to accurately predict hepatocellular carcinoma (HCC) survival; however, pathomics models can predict EZH2 expression and HCC prognosis. This study aimed to investigate the relationship between pathomics features and EZH2 expression for predicting overall survival of patients with HCC.

Methods: We analyzed 267 patients with HCC from the Cancer Genome Atlas database, with available pathological images and gene expression data. RNA sequencing data were divided into high and low EZH2 expression groups for prognosis and survival analysis. Pathological image features were screened using mRMR_RFE. A pathological model was constructed using a gradient boosting machine (GBM) algorithm, and efficiency evaluation and survival analysis of the model were performed. The R package "survminer" took the pathomics score (PS) cutoff value of 0.4628 to divide the patients into two groups: high and low PS expression. Survival analyses included Kaplan-Meier curve analysis, univariate and multivariate Cox regression analyses, and interaction tests. Potential pathomechanisms were explored through enrichment, differential, immune cell infiltration abundance, and gene mutation analyses.

Result: EZH2 was highly expressed in tumor samples but poorly expressed in normal tissue samples. Univariate and multivariate Cox regression analyses revealed that EZH2 was an independent risk factor for HCC (hazard ratio [HR], 2.792 and 3.042, respectively). Seven imaging features were selected to construct a pathomics model to predict EZH2. Decision curve analysis showed that the model had high clinical utility. Multivariate Cox regression analysis showed that high PS expression was an independent risk factor for HCC prognosis (HR, 2.446). The Kaplan-Meier curve showed that high PS expression was a risk factor for overall survival.

Conclusion: EZH2 expression can affect the prognosis of patients with liver cancer. Our pathological model could predict EZH2 expression and prognosis of patients with HCC with high accuracy and robustness, making it a new and potentially valuable tool.