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Figure 1. (A) In silico analysis of PER2 mRNA expression in LIHC samples (purple boxplot) from TCGA cohort (obtained from RNAseq) compared with normal liver tissues (grey boxplot); (B) In silico analysis of PER2 mRNA expression in different stages of LIHC; (C) and (D) In silico analysis of PER2 mRNA expression in HCC cell lines from CCLE based on a dataset posted in 2022; (C) A comparison of PER2 mRNA expression between HCC and hepatoblastoma cell lines; and (D) a comparison of PER2 mRNA expression in HCC cell lines derived from human primary HCC, HCC cell lines with no clear origin, and HCC cell lines derived from human HCC metastasis; (E) Kaplan-Meier curve to assess the overall survival rate of patients with HCC depending on the PER2 gene expression; (F) SOR effect on cell line proliferation. Cell proliferation evaluated by DNA assay in PLC/PRF/5 cells: parental (black bars) and SorR (gray bars). The data presented are mean ± SEM of three independent experiments. *P < 0.05, ***P < 0.001 between groups; (G) PER2 mRNA expression in PLC/PRF/5 parental, PLC/PRF/5 EveR, PLC/PRF/5 SorR, PLC/PRF/5 PER2 KD, and PLC/PRF/5 PER2 KO relative to HPRT housekeeping gene. *P < 0.05; **P < 0.01; ***P < 0.001; (H) PER2 protein expression in PLC/PRF/5 parental, PLC/PRF/5 PER2 KD, and PLC/PRF/5 PER2 KO with related densitometry. ****P < 0.0001. PER2: Period 2; LIHC: Liver Hepatocellular Carcinoma; CCLE: Cancer Cell Line Encyclopaedia; TCGA: The Cancer Genome Atlas; HCC: hepatocellular carcinoma; SOR: sorafenib; SEM: standard error of the mean; EveR: everolimus-resistant; SorR: sorafenib-resistant; KD: knockdown; KO: knockout; HPRT: Hypoxanthine Phosphoribosyltransferase 1.