(A) Y5R mRNA levels in primary human hepatocytes (PHH) (n = 5) compared with human HCC cells Hep3B (n = 3), HepG2 (n = 3), Huh-7 (n = 4), and PLC (n = 3). (B) Y5R Western blot analysis: representative image (PHHs from 2 donors [d#1, d#2]) and quantification of protein levels (PHHs [n = 4] compared with Hep3B [n = 3], HepG2 [n = 3], Huh-7 [n = 3], PLC [n = 5]). (C and D) HCC cells transfected with siRNA pools against Y5R (si-Y5R) or a control siRNA pool (Control). (C) Coimmunofluorescence (Y5R, Ki-67) images (20-fold original magnification; n = 2). (D) Representative proliferation curves and quantification (n = 3) (box-and-whisker plots [min to max]). (E) Correlated Y5R and cyclin D1 mRNA (human HCC tissues; n = 17). (F) Clonogenicity (colony numbers, sizes, representative images) of PLC cells after RNAi-mediated Y5R knockdown (n = 3). (G) SurvExpress analysis of Y5R expression and overall survival (TCGA data; n = 381). Computational stratification (low-risk and high-risk groups) based on prognostic index. (H and I) Comparison of survival of patients with low (n = 17) and high (n = 39) Y5R expression (H) and tumor stages of patients with low (n = 25) and high (n = 92) Y5R expression (I) based on IHC analysis of HCC tissue microarray samples. Data are presented as mean ± SEM. Statistical significance was determined by ordinary 1-way ANOVA and Dunnett’s multiple-comparisons test (A and B); 2-tailed, unpaired t test (D and F); Pearson correlation (E); 2-sided Fisher’s exact test, Spearman’s correlation, and uni- and multivariate analysis (ordinal regression analysis, link function: logit) (H and I); and log-rank testing and hazard ratio estimates (G). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.