circ0006646 serves as a robust prognostic biomarker for post-transplant tumor recurrence and survival in hepatocellular carcinoma patients.

Background: Tumor recurrence severely impacts the prognosis of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). We aimed to explore novel and robust biomarkers for precise prediction of tumor recurrence and prognosis following LT.

Methods: Cancerous tissues of 252 HCC patients who underwent LT across three centers were included in the study. Tissue microarrays and in situ hybridization were utilized to assess the circ0006646 level. Kaplan-Meier method along with the log-rank test were performed to analyze overall survival and recurrence-free survival. To identify prognostic factors, particularly related to tumor recurrence, we conducted univariate and multivariate Cox regression analyses. Nomogram was constructed to predict the risk of tumor recurrence after LT and subsequently the efficacy of the nomogram was validated.

Results: Elevated circ0006646 levels in HCC were associated with reduced survival and increased recurrence rates following LT (5-year overall survival: 60.4 % vs. 29.2 %, P < 0.01; 5-year recurrence-free survival: 63.0 % vs. 42.3 %, P < 0.001). High circ0006646 expression was significantly correlated with higher Child-Pugh grade (P = 0.040), larger total tumor diameter (P = 0.033), and beyond the Milan criteria (P = 0.033). Cox regression analysis unveiled that circ0006646 expression score, preoperative transarterial chemoembolization (TACE), positive HBsAg status, poor tumor differentiation and beyond the Hangzhou criteria were independent risk factors for post-transplant tumor recurrence, leading to the development of a novel nomogram for precise prediction. The nomogram demonstrated a reasonable prognostic effectiveness (area under the receiver operating characteristic curve = 0.7636, C-index = 0.745) and outperformed conventional models like the Milan criteria. Besides, the inclusion of circ0006646 enhanced the precision of the Milan and Hangzhou criteria. Moreover, circ0006646 served as a potent biomarker in alpha fetoprotein (AFP)-negative HCC undergoing LT.

Conclusions: circ0006646 is a novel and robust prognostic biomarker for predicting post-transplant survival and tumor recurrence in HCC patients. A nomogram integrating circ0006646 stands as a valuable prognostic instrument in LT for HCC.