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

doi:10.12122/j.issn.1673-4254.2026.01.19

Abstract

Abstract:

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

Key words: hepatocellular carcinoma, ERI3, metastasis, prognosis

Xinli ZHAO, Haojie WANG, Yinchun SONG, Shuai YUAN, Zhen ZHANG, Xingqi ZHOU, Shanshan LI, Xian LI, Feng LI. ERI3 expression is elevated in hepatocellular carcinoma and correlates with poor patient prognosis[J]. Journal of Southern Medical University, 2026, 46(1): 175-182.

Figures/Tables 8

Fig.1 Differential expression of ERI3 between normal (n=50) and hepatocellular carcinoma (HCC) tissues (n=377). ***P<0.001.

Fig.2 Protein-protein interaction network (A) and the functional association network (B).

Fig.3 Kaplan-Meier curves for overall survival, disease-specific survival, and progression-free survival in HCC patients (n=377).

Fig.4 Correlation between ERI3 expression levels and TNM stage of HCC. *P<0.05, **P<0.01, ***P<0.001 (normal n=50, Hcc n=377).

Fig.5 Tumor immune infiltration analysis. A: Lollipop chart showing the correlation between ERI3 expression and infiltration levels of 24 immune cell types. B, C: Scatter plots showing the correlation between ERI3 expression and abundance of Th2 and Th17 cells. D: Scatter plot of the correlation between ERI3 expression and B cells in HCC. n=377, *P<0.05, **P<0.01, ***P<0.001.

Fig.6 Nomogram and calibration curve. A: Prognostic nomogram integrating ERI3 expression and clinicopathological parameters. B: Calibration curves for 1-, 3-, and 5-year survival probability of HCC patients (n=373).

Tab.1 Univariate and multivariate Cox proportional hazards regression analysis of overall survival in HCC patients

Variable	n	Univariate analysis		Multivariate analysis
Variable	n	HR (95% CI)	P	HR (95% CI)	P
Pathologic T stage	370
T1&T2/T3&T4	277/93	2.598 (1.826-3.697)	<0.001	2.467 (1.587-3.836)	<0.001
Pathologic N stage	258
N0/N1	254/4	2.029 (0.497-8.281)	0.324
Pathologic M stage	272
M0/M1	268/4	4.077 (1.281-12.973)	0.017	1.739 (0.531-5.697)	0.361
Gender	373
Female/Male	121/252	0.793 (0.557-1.130)	0.200
Age	373
≤60/>60	177/196	1.205 (0.850-1.708)	0.295
Weight	345
≤70/>70	184/161	0.941 (0.657-1.346)	0.738
AFP (ng/mL)	279
≤400/>400	215/64	1.075 (0.658-1.759)	0.772
Fibrosis ishak score	214
0	75
1, 2&3, 4	59	0.823 (0.436-1.554)	0.548
5&6	80	0.737 (0.410-1.324)	0.307
Vascular invasion	317
No/Yes	208/109	1.344 (0.887-2.035)	0.163
ERI3	373
Low/High	186/187	2.307 (1.608-3.310)	<0.001	1.987 (1.256-3.142)	0.003

Fig7 ERI3 knockdown inhibits proliferation, invasion, and migration of HCC cells in vitro. A: PCR for assessing the efficiency of ERI3 knockdown. B: Colony formation assay for assessing cell proliferation. C: Transwell assay for assessing cell migration and invasion (Original magnification: ×10). D: ERI3 knockdown of ERI3 impairs wound healing in HCC Cells (×200). n=3, *P<0.05, **P<0.01 vs shNC group.

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