Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in HCC

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. While curative resection is pivotal, high postoperative recurrence rates remain a major challenge. Adjuvant immune checkpoint inhibitors (ICIs) show promise in improving outcomes, but biomarkers to identify patients who will benefit are lacking. Current clinicopathological risk factors for minimal residual disease (MRD) are suboptimal in sensitivity and specificity.

Circulating tumor DNA (ctDNA) analysis, reflecting real-time tumor dynamics, offers a promising approach for MRD detection. This study focuses on the methylation status of GNB4 and Riplet-genes located within HCC-associated CpG islands-using a bespoke bisulfite-conversion and qPCR assay to sensitively detect methylated alleles, thereby enabling MRD monitoring.

To clinically validate this approach, we will conduct a prospective, multicenter cohort study assessing the predictive value of serial \*GNB4/Riplet\* methylation testing for recurrence and adjuvant therapy benefit.