J Cancer 2021; 12(23):7190-7200. doi:10.7150/jca.59612 This issue

Research Paper

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

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 Fan1,2, Jian Zhou1,2,3✉, Jie Hu1✉

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.
# Equal contributor.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Huang A, Guo DZ, Wang YP, Yang GH, Sun QM, Zhang X, He YF, Song K, Huang XW, Yang XR, Fan J, Zhou J, Hu J. Plasma MicroRNA Panel Predicts Early Tumor Recurrence in Patients with Hepatocellular Carcinoma after Liver Transplantation. J Cancer 2021; 12(23):7190-7200. doi:10.7150/jca.59612. Available from https://www.jcancer.org/v12p7190.htm

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Abstract

Graphic 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: hepatocellular carcinoma, liver transplantation, early recurrence, liquid biopsy, microRNA.