LGR5 and hepatocellular carcinoma: Particularly, exposure to genotoxic stressors, such as regorafenib, sorafenib, cisplatin, and gemcitabine, markedly increased the levels of HCC stemness markers (CD13high, CD24high, CD44high, CD90high, CD133high, EpCAM, ICAM-1, LGR5, MAEL, Cripto-1, and Oct4high) and calcium-mediated and survival-related target genes (ATP2A isoforms and B-cell lymphoma 2 (Bcl-2)) in drug-resistant HCC cells compared with those in drug-sensitive HCC cells (Figure 2B).