Plasma EIF2C1 Cell-Free DNA as a Novel Biomarker for Hepatocellular Carcinoma Diagnosis and Risk Stratification - 14/03/26

Doi : 10.1016/j.clinre.2026.102808

Yang Xiao ^a,^b,^{^{†
These authors have contributed equally to this work.}}, Ning Li ^a,^{^{†
These authors have contributed equally to this work.}}, Liyan Jiang ^a,^b, Hongling Wang ^a, Linlin Xu ^a, Huoying Chen ^a,^c,^⁎

^a Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, China.

^b The First Clinical Medicine School, Guilin Medical University, Guilin, China

^c Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Guangxi Key Laboratory of Multimodal Biomarkers and Precision Diagnosis, Guilin Medical University, Guilin 541199, China.

^⁎ Correspondence Huoying Chen, Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, PR China. Tel: 0086-13788749936. Fax: 0086-773-5595046 Department of Laboratory Medicine The Second Affiliated Hospital of Guilin Medical University Guilin 541199 PR China

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Highlights

•	The levels of EIF2C1 in the HCC group were higher than the healthy control group.
•	EIF2C1 levels were associated with the clinical stage of HCC, cirrhosis.
•	EIF2C1 levels were associated with liver function and tumor metastasis.
•	The combined detection of EIF2C1 with AFP enhanced diagnosis value.

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Abstract

Aim

Hepatocellular Carcinoma (HCC) remains a leading cause of cancer-related death, particularly in China, with limited diagnosis sensitivity and specificity. Circulating cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker. Eukaryotic Translation Initiation Factor 2C1 ( EIF2C1) , commonly used as a reference gene in digital PCR, reflects total cfDNA burden. This study aimed to evaluate the diagnostic value of plasma EIF2C1 -normalized cfDNA levels for HCC detection and to explore its association with disease severity and metastatic features at diagnosis.

Methods

Plasma samples from 101 HCC patients and 90 healthy controls were analyzed using Real-Time Quantitative PCR (RT-qPCR) to quantify EIF2C1 levels, employing two sets of primers and probes ( EIF2C1 -1 and EIF2C1 -2). Clinical data and tumor markers were collected to evaluate the association of EIF2C1 levels with disease severity and metastatic risk.

Results

EIF2C1 levels were significantly elevated in HCC patients and correlated inversely with hepatic synthetic markers while positively associating with tumor progression indicators. Higher EIF2C1 expression was linked to advanced stage, cirrhosis, liver dysfunction, and metastasis. The combined models of EIF2C1 and alpha-fetoprotein (AFP) demonstrated enhanced discriminatory ability compared to individual markers ( EIF2C1 -1 + AFP: AUC=0.744, 95% CI: 0.642-0.845; EIF2C1 -2 + AFP: AUC=0.764, 95% CI: 0.662-0.866). Furthermore, elevated EIF2C1 levels were significantly associated with the presence of metastasis (OR=20.87, 95% CI: 5.13-84.92).

Conclusion

Plasma EIF2C1 levels show promise as a complementary diagnostic and risk-stratification biomarker in HCC. Its combination with AFP improves the identification of metastatic disease at diagnosis, potentially aiding initial clinical management .

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Keywords : liver cancer, cell-free DNA, biomarker, risk prediction