What question did this study set out to answer?

The aim is to assess the diagnostic value of EIF2C1-normalized cfDNA levels in detecting HCC and its relation to disease severity.

March 16, 2026Open Access

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

Key Points

The aim is to assess the diagnostic value of EIF2C1-normalized cfDNA levels in detecting HCC and its relation to disease severity.
Analyzed plasma samples from 101 HCC patients and 90 healthy controls.
Quantified EIF2C1 levels using Real-Time Quantitative PCR with two primer sets.
Collected clinical data and tumor markers to evaluate EIF2C1's association with disease features.
EIF2C1 levels were significantly higher in HCC patients compared to healthy controls.
Elevated EIF2C1 was associated with advanced clinical stage, cirrhosis, and liver dysfunction.
Combined models of EIF2C1 and AFP showed enhanced diagnostic value, with AUC values of 0.744 and 0.764.

Abstract

• 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. 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. 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. 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). 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 .

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

Key Points

Abstract

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