Prognostic MicroRNA Fingerprints Predict Recurrence of Early-Stage Hepatocellular Carcinoma Following Hepatectomy

Abstract

Purpose: This study aims to develop liquid biopsy assays for early HCC diagnosis and prognosis. Methods: Twenty-three microRNAs were first consolidated as a panel (HCCseek-23 panel) based on their reported functions in HCC development. Serum samples were collected from 103 early-stage HCC patients before and after hepatectomy. Quantitative PCR and machine learning random forest models were applied to develop diagnostic and prognostic models. Results: For HCC diagnosis, HCCseek-23 panel demonstrated 81% sensitivity and 83% specificity for identifying HCC in the early-stage; it showed 93% sensitivity for identifying alpha-fetoprotein (AFP)-negative HCC. For HCC prognosis, the differential expressions of 8 microRNAs were significantly associated with disease-free survival (DFS) (Log-rank test p-value = 0.001). Further model improvement using these HCCseek-8 panel in combination with serum biomarkers (i.e. AFP, ALT, and AST) demonstrated a significant association with DFS (Log-rank p-value = 0.011 and Cox proportional hazards analyses p-value = 0.002). Conclusion:To the best of our knowledge, this is the first report to integrate circulating miRNAs, AST, ALT, AFP, and machine learning for predicting DFS in early HCC patients undergoing hepatectomy. In this setting, HCCSeek-23 panel is a promising circulating microRNA assay for diagnosis, while HCCSeek-8 panel is promising for prognosis to identify early HCC recurrence.

Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review

“…For patients with hepatitis B virus-related HCC who undergo LR, Cho et al [ 98 ] support circulating levels of miR-26a and miR-29a as predictors of poor DFS and OS. Recently, Wong et al [ 10 ] combined quantitative PCR and artificial intelligence to integrate circulating microRNA with laboratory tumor characteristics and create a diagnostic and predictive model of DFS in patients undergoing LR. These authors identified a panel of eight microRNAs (which they termed the HCC seek-8 panel) that, in combination with serum biomarkers, was significantly associated with DFS.…”

“…Specifically, three categories of markers have been identified: (i) markers measured in liquid biopsy specimens, (ii) gene signatures, and (iii) markers associated with inflammation. A few markers not in any of these categories have also been identified, including prothrombin induced by vitamin K absence-II (PIVKA-II), programmed cell death protein-1 (PD-1), microRNAs, and proteins in urinary exosomes (Figure 1) [8][9][10][11]. Unfortunately, not all of the aforementioned markers are readily available in clinical practice, and their reproducibility is unclear.…”