Characteristics of liver cancer stem cells and clinical correlations

• Distinct liver CSC origins and their correlation with liver cancer heterogeneity are discussed.
• Advances in liver CSC surface markers and functional isolation approaches are summarized.
• Most recent progress in the genetic and epigenetic regulation of liver CSCs is concluded.
• Clinical application of liver CSCs in liver cancer diagnosis and treatment is comprehensively reviewed.

Liver cancer is an aggressive malignant disease with a poor prognosis. Patients with liver cancer are usually diagnosed at an advanced stage and thus miss the opportunity for surgical resection. Chemotherapy and radiofrequency ablation, which target tumor bulk, have exhibited limited therapeutic efficacy to date. Liver cancer stem cells (CSCs) are a small subset of undifferentiated cells existed in liver cancer, which are considered to be responsible for liver cancer initiation, metastasis, relapse and chemoresistance. Elucidating liver CSC characteristics and disclosing their regulatory mechanism might not only deepen our understanding of the pathogenesis of liver cancer but also facilitate the development of diagnostic, prognostic and therapeutic approaches to improve the clinical management of liver cancer. In this review, we will summarize the recent advances in liver CSC research in terms of the origin, identification, regulation and clinical correlation.