Circulating miRNAs combined with AFP improve diagnostic accuracy for HBV-associated hepatocellular carcinoma

Early detection of hepatocellular carcinoma (HCC) remains challenging due to the suboptimal diagnostic accuracy of alpha-fetoprotein (AFP). Circulating microRNAs (miRNAs), given their blood stability and role in cancer biology, have emerged as promising non-invasive biomarkers. This study aimed to assess the diagnostic value of serum miR-21-5p, miR-34a-5p, and miR-30d-3p, individually and in combination with AFP, for distinguishing HBV-related HCC from chronic hepatitis B (CHB) and liver cirrhosis (LC) in a Vietnamese patient cohort.

A total of 450 participants were recruited, including 150 patients with HBV-related HCC, 150 with HBV-related LC, and 150 with CHB. Serum miRNA expression levels were quantified using RT-qPCR and were assessed for the diagnostic performance using receiver operating characteristic (ROC) curve.

Expression of circulating miR-21-5p, miR-34a-5p, and miR-30d-3p was significantly upregulated in HCC patients compared to those with CHB and LC (p < 0.001). In which, miR-21-5p presented the highest relative increase, with a 5.43-fold elevation versus CHB. Generalized linear models incorporating single miRNAs (GLM1-3) adjusted for age and gender achieved AUCs = 0.74-0.75 (HCC vs LC); 0.82-0.83 (HCC vs. non-HCC), and 0.9-0.92 (HCC vs. CHB). Notably, the 3-miRNA model adjusted for age and gender (GLM7) demonstrated strong discriminatory power: AUC = 0.92 (HCC vs. CHB), 0.75 (HCC vs. LC), and 0.83 (HCC vs. non-HCC). When AFP was integrated, diagnostic performance improved markedly across all comparisons: AUC = 0.97 (HCC vs. CHB), 0.84 (HCC vs. LC), and 0.91 (HCC vs. non-HCC).

Combining circulating miR-21-5p, miR-34a-5p, and miR-30d-3p with AFP significantly enhances diagnostic accuracy for HBV-related HCC, supporting their utility as complementary non-invasive biomarkers for early screening.