Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma

Kun Ma; Jiayun Liu; Youjin Wang; Yubin Zhong; Zhenfeng Wu; Ruiying Fan; Shanfeng Guo

doi:10.21037/jgo-20-509

Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma

J Gastrointest Oncol. 2020 Dec;11(6):1350-1363. doi: 10.21037/jgo-20-509.

Authors

Kun Ma¹, Jiayun Liu², Youjin Wang¹, Yubin Zhong³, Zhenfeng Wu², Ruiying Fan⁴, Shanfeng Guo¹

Affiliations

¹ Department of Interventional Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
² Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
³ Department of General Surgery, Yixing People's Hospital, Yixing, China.
⁴ Department of Medical Oncology, Taikang Xianlin Drum Tower Hospital, Nanjing, China.

Abstract

Background: Our study aims to investigate changes in cell-free DNA (cfDNA) concentration and integrity in primary hepatocellular carcinoma (PHC) patients before and after transcatheter arterial chemoembolization (TACE) treatment and their influence on the evaluation of prognosis of the disease.

Methods: A total of 84 PHC patients admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from December 2016 to December 2017 were included as the study group, while 55 healthy people served as the control group. Plasma cfDNA concentration and integrity were determined using qRT-PCR. The correlation between cfDNA concentration/integrity and clinical characteristics of PHC patients were analyzed. A ROC curve was used to investigate the sensitivity and specificity of cfDNA as detection indices. Univariate and multivariate analyses were used to analyze factors affecting recurrence in PHC patients and compare recurrence-free survival (RFS) of PHC patients with high cfDNA expression and low cfDNA expression.

Results: Plasma cfDNA concentration and integrity were significantly higher in PHC patients before TACE treatment than in healthy people and significantly lower after treatment than before (P<0.05). The cfDNA concentration was significantly correlated with tumor size, lymph node metastasis, TNM stage, and BCLC stage, while cfDNA integrity was significantly correlated with tumor size, TNM stage, and BCLC stage (P<0.05). ROC results showed that the area under the curve (AUC) value of cfDNA concentration was the largest, with an optimal cut-off of 10.51 ng/mL. Multivariate regression analysis for COX showed that the TNM stage, cfDNA concentration, and AFP were independent risk factors that affected PHC patients' survival.

Conclusions: Plasma cfDNA concentration in PHC patients is more sensitive and specific than any other tumor marker. It is an independent risk factor for PHC patients treated with TACE. Therefore, it is hypothesized cfDNA is a potential biomarker for prognostic evaluation of PHC patients treated with TACE.

Keywords: Primary hepatocellular carcinoma (PHC); cell-free DNA (cfDNA); independent risk factor; prognosis; transcatheter arterial chemoembolization (TACE).