Fig. 1

Oncogenic alterations in the expression of CBS, CTH, and SLC7A11 genes in patients with hepatocarcinoma. A, Schematic illustrating the cysteine metabolic pathways. Cysteine is synthesized from methionine or converted from cystine that is uptaken by xCT from the extracellular fluid. Cysteine is also used for glutathione synthesis. B, Differences in the expression of CBS, CTH, and SLC7A11 genes in the liver and hepatic tumors. RNA-seq data obtained from patients with hepatocarcinoma were analyzed using the TNMplot database. P-values were calculated using the Mann–Whitney U-test. C, Tumor grade-dependent expression of CBS, CTH, and SLC7A11 genes in liver hepatocellular carcinoma (LIHC) patients. TCGA samples were analyzed using the UALCAN database. Grade 1, well-differentiated (low grade); grade 2, moderately differentiated (intermediate grade); grade 3, poorly differentiated (high grade); grade 4, undifferentiated (high grade). ***P < 0.001, **P < 0.01, *P < 0.05; significant difference compared with the normal group (unpaired t-test). D, Prognostic significance of the expression for CBS, CTH, and SLC7A11 genes in LIHC patients analyzed using the Kaplan–Meier plotter database. Hazard ratios with 95% confidence intervals and log-rank P-values were calculated using Kaplan–Meier plots. E, The mRNA levels of genes involved in cysteine metabolism in the human normal hepatocytes, HepG2 cells, and HepaRG cells. The expression levels were normalized to those of 18s. The values in the human normal liver were set at 1.0. Each value represents the mean with S.D. (n = 3). **P < 0.01; significant difference between the indicated groups (F_2,6 = 595.045, P < 0.001 for CBS; F_2,6 = 1572.452, P < 0.001 for CTH; F_2,6 = 14.902, P = 0.005 for SLC7A11; ANOVA with Tukey–Kramer’s post hoc test)