Establishing a miRNA panel for hepatocellular carcinoma screening through a multicenter study

Most patients with hepatocellular carcinoma (HCC) are often diagnosed at advanced stages, limiting the effectiveness of curative treatments. In a multicenter study involving 522 patients with HCC and liver cirrhosis, predominantly with hepatitis B virus infection, we evaluated plasma microRNAs (miRNAs) as potential liquid biopsy biomarkers for early HCC screening. Significant upregulation of 18 miRNAs in HCC patients was confirmed across three stages. We conducted a meta-analysis integrating our results with existing literature based on pooled effect size, successfully confirming the upregulation of 4 miRNAs in our findings. Employing an explainable machine learning approach, we established a 5-miRNA panel (miR-361-5p+ miR-130a-3p+ miR-27a-3p+ miR-30d-5p+ miR-193a-5p) with alpha-fetoprotein (AFP) for HCC screening. This combined panel demonstrated superior diagnostic performance compared to AFP alone (AUC: 0.924 vs. 0.794; p < 0.001) in distinguishing HCC patients in the testing and validation set, highlighting its potential as a promising minimally invasive screening method for HCC.