Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer

Wei Zhao; Lige Qiu; Huajiang Liu; Ying Xu; Meixiao Zhan; Wei Zhang; Yongjie Xin; Xu He; Xiangyu Yang; Jing Bai; Jing Xiao; Yanfang Guan; Qiyang Li; Lianpeng Chang; Xin Yi; Yong Li; Xudong Chen; Ligong Lu

doi:10.21037/jgo-20-409

Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer

J Gastrointest Oncol. 2020 Oct;11(5):1065-1077. doi: 10.21037/jgo-20-409.

Authors

Wei Zhao¹, Lige Qiu^{1

2}, Huajiang Liu³, Ying Xu⁴, Meixiao Zhan¹, Wei Zhang², Yongjie Xin¹, Xu He¹, Xiangyu Yang¹, Jing Bai⁵, Jing Xiao¹, Yanfang Guan^{4

5}, Qiyang Li², Lianpeng Chang⁵, Xin Yi⁵, Yong Li¹, Xudong Chen², Ligong Lu¹

Affiliations

¹ Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, China.
² 2 Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
³ Department of Intervention Therapy, The First Affiliated Hospital of Hainan Medical University, Haikou, China.
⁴ Department of Computer Science and Technology, School of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
⁵ Geneplus-Beijing Institute, Beijing, China.

Abstract

Background: Imaging and alpha fetoprotein (AFP) measurement are used as surveillance methods during interventional therapy in patients with unresectable liver cancer, but their accuracy has been challenged in patients receiving drug perfusion therapy. Circulating tumor DNA (ctDNA) can reflect tumor load and treatment efficacy. Studies of the prognostic value of ctDNA in unresectable liver cancer are needed.

Methods: Forty-two patients with unresectable liver cancer were prospective enrolled in this study. Pre-treatment, in-treatment plasma samples and available matched tissue samples were collected. Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors.

Results: Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors revealed that the most frequently mutated genes in ctDNA were TP53 (52.4%) and TERT (35.7%). The ctDNA abundance was more closely correlated with tumor size than the AFP level and was also related to BCLC stage (P<0.001). Gene mutations profile in ctDNA with progressed disease. PD patients were enriched in TP53 mutation group compared with TP53 wildtype group (P=0.0221). Moreover, interventional therapy was more effective in patients without TP53 mutation (OS: P=0.0589; PFS: 0.0411). The dynamic change of ctDNA showed consistent or more sensitivity than imaging for evaluating treatment response. The tumor mutation burden was highly consistent between tissue and blood samples (P<0.0001).

Conclusions: ctDNA was a reliable biomarker to assist in diagnosis and evaluation of prognosis and treatment efficacy in advanced liver cancer. Considering that biopsy is unnecessary when advanced liver cancer is diagnosed, ctDNA may be an ideal biomarker for evaluating tumor mutation burden prior to immunotherapy.

Keywords: Primary liver cancer (PLC); circulating cell-free DNA; interventional therapy; treatment efficacy; tumor mutation burden.