EMT-Related Gene Signature: A New Method for Personalized Risk Assessment in Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, accounting for more than 700,000 deaths annually. Epithelial-mesenchymal transition (EMT) is posited to contribute to HCC progression. We, therefore, aimed to elucidate the relationship between EMT-related gene (ERG) expression and prognosis in patients with HCC.

Univariate and multivariate Cox regression analyses were performed to identify prognostic-related differentially expressed EMT-related genes (DE-ERGs). Time-dependent receiver operating characteristic and Kaplan-Meier curves were used to assess the prognostic performance of the EMT-related signature. pRRophetic R package was used to evaluate sorafenib sensitivity in the GSE14520 cohort. Gene expression in Huh7 and L02 cell lines was detected by real-time PCR and Western blotting. Differential expression of the three genes between HCC tissues and normal tissues was validated using immunohistochemical analyses.

Of the 76 identified DE-ERGs, 29 were associated with overall survival. Three prognosis-related ERGs (GOLM1, SOX4, and CD14) were screened out by multivariate Cox regression. A gene signature was identified based on the three prognostic-related ERGs. HCC patients with a low-risk score had a better prognosis and were more sensitive to sorafenib compared to those with a high-risk score. Moreover, we further confirmed increased expression of GOLM1 and SOX4, and decreased expression of CD14, in liver cancer cell line and HCC tissue.

The results of the present study demonstrate the utility of an ERG signature as a potential biomarker informing prognosis in patients with HCC, which may contribute to the implementation of personalized therapies.