Plasma MicroRNA Panel Predicts Early Tumor Recurrence in Patients with Hepatocellular Carcinoma after Liver Transplantation

Ao Huang; De-Zhen Guo; Yu-Peng Wang; Guo-Huan Yang; Qi-Man Sun; Xin Zhang; Yi-Feng He; Kang Song; Xiao-Wu Huang; Xin-Rong Yang; Jia Fan; Jian Zhou; Jie Hu

doi:10.7150/jca.59612

Plasma MicroRNA Panel Predicts Early Tumor Recurrence in Patients with Hepatocellular Carcinoma after Liver Transplantation

J Cancer. 2021 Oct 22;12(23):7190-7200. doi: 10.7150/jca.59612. eCollection 2021.

Authors

Ao Huang¹, De-Zhen Guo¹, Yu-Peng Wang¹, Guo-Huan Yang¹, Qi-Man Sun¹, Xin Zhang¹, Yi-Feng He¹, Kang Song¹, Xiao-Wu Huang¹, Xin-Rong Yang¹, Jia Fan^{1

2}, Jian Zhou^{1

2

3}, Jie Hu¹

Affiliations

¹ Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education; Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
² Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
³ State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.

Abstract

Background: This study aimed to evaluate the role of plasma microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) for prediction and surveillance of early tumor recurrence in hepatocellular carcinoma (HCC) patients who had undergone liver transplantation (LT). Methods: The expression of plasma microRNA panel was assayed in 193 HCC patients (training cohort, n =151; validation cohort, n = 42). Sensitivity and specificity for detecting post-transplant HCC recurrence, and the relationship of microRNA panel expression with clinical characteristics were analyzed accordingly. The prognostic value of microRNA panel was compared with that of AFP (alpha-fetoprotein) and DCP (Des-gamma-carboxyprothrombin). Cox regression analyses were used to evaluate independent prognostic factors. Results: In the training cohort, the rate of positive plasma microRNA panel status at 7-14 days after LT (late phase; 44.2%) decreased than that before (76.2%, P < 0.001) and 1-6 days after LT (early phase; 78.5%, P < 0.001). At late phase, positive microRNA panel status correlated with higher early tumor recurrence rate (one year after LT) than negative status (45.9% vs 10.7%; P < 0.001). Patients with persistent positive microRNA panel status both before and after LT had the highest early tumor recurrence rate in this cohort (54.9%, P < 0.001). The results were consistent in the validation cohort. Cox regression analysis found that positive plasma microRNA panel status at late phase was the only independent risk factor for early recurrence (HR: 4.903, 95% CI = 2.195 - 10.951; P < 0.001). Dynamic monitoring demonstrated plasma microRNA panel status changed from negative to positive earlier than AFP and DCP upon recurrence, and the median time between positivity of plasma microRNA and imaging evidence of recurrence was 2.4 (0.5-10.0) months. Conclusions: Plasma microRNA panel could be a noninvasive biomarker for prediction and surveillance of early tumor recurrence in HCC patients who have undergone LT.

Keywords: early recurrence; hepatocellular carcinoma; liquid biopsy; liver transplantation; microRNA..