Junsheng Zhao ^1* Zekai Hu ¹ Xiaoping Zheng ² Yajie Lin ¹ Xiao Liu ¹ Junjie Zhang ¹ Jing Peng ³ Hainv Gao ^4*

• ¹ Zhejiang Shuren University, Hangzhou, China
• ² Hangzhou Tongchuang Medical Laboratory, Hangzhou, Jiangsu Province, China
• ³ Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
• ⁴ Shulan Hospital, Hangzhou, Jiangsu Province, China

Hepatocellular Carcinoma (HCC) is a malignant tumor with high morbidity and mortality worldwide, which represents a serious threat to human life, health and quality of life. Blood-based detection is essential for HCC screening, early diagnosis, prognosis evaluation, and surveillance. Current non-invasive detection strategy including serum alpha-fetoprotein (AFP), ultrasound, computerized tomography, and magnetic resonance imaging. The limited specificity of an AFP and the dependence on operator experience and diagnostic personnel for ultrasound have constrained their utility in early HCC diagnosis. In recent years, with the development of various detection technologies, there has been an increasing focus on exploring blood-based detection markers for HCC. The types of markers include protein markers, DNA mutation, DNA epigenetic modification, mRNA, miRNA, and so on.However, numerous methodological and biological factors limit the clinical sensitivity and generalization performance of these new biomarkers. In this review, we describe the state-of-the-art technologies for cfDNA analysis, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve HCC diagnostics and patient care.