[ERI3 expression is elevated in hepatocellular carcinoma and correlates with poor patient prognosis]

To analyze the expression pattern of Exoribonuclease Family Member 3 (ERI3) in hepatocellular carcinoma (HCC) tissues and its influences on long-term prognosis and cancer cell metastasis.

Based on the TCGA-LIHC dataset (including 377 HCC and 50 adjacent normal tissues), the differential expression of ERI3 was analyzed using DESeq2, and the results were validated using immunohistochemical data from the HPA database. A protein-protein interaction network was constructed using STRING and GeneMANIA. The prognostic value of ERI3 was assessed by Cox regression and Kaplan-Meier (KM) survival analyses, its diagnostic efficacy evaluated by ROC curve analysis, and its correlation with immune infiltration analyzed with ssGSEA algorithm. A nomogram prognostic model was established using multivariate Cox regression. For functional validation of ERI3 in vitro, a human HCC cell line SMMC-7721 with ERI3 knockdown was constructed, and the changes in cell proliferation, migration, and invasion were assessed using CCK-8, colony formation, wound healing, and Transwell assays.

ERI3 was significantly overexpressed in HCC tissues (P<0.001) and its expression levels increased progressively with advanced TNM stages (T1-T4: P<0.001). In HCC patients, high ERI3 expressions were correlated with a reduced overall survival (HR=2.86, 95% CI: 1.68-4.88; P<0.001), disease-specific survival (HR=2.27, P=0.013), and progression-free interval (HR=1.83, P=0.012). Diagnostic efficacy analysis revealed an AUC of 0.955 (95% CI: 0.931-0.978) for ERI3. Immune infiltration studies demonstrated a positive correlation of ERI3 expression level with Th2 cells (r=0.340, P<0.001) and a negative correlation with Th17 cells (r=-0.284, P<0.001). Multivariate Cox regression analysis identified ERI3 as an independent prognostic factor for HCC (HR=1.987, P=0.003), and the constructed nomogram showed a good predictive accuracy (C-index=0.668). In SMMC-7721 cells, ERI3 knockdown significantly suppressed cell proliferation, migration, and invasion.

ERI3 overexpression promotes HCC cell proliferation, migration, and invasion and is strongly linked to a poor prognosis of the patients.