T cell exhaustion markers in hepatitis C virus-related hepatocellular carcinoma: Expression patterns and prognostic significance in an Egyptian cohort

Table 2 Immune checkpoint expression and T-cell profiles across study groups, mean ± SD/median (interquartile range)

Parameter	HCC (n = 50)	Cirrhosis (n = 50)	HCV (n = 50)	Control (n = 50)	8F/Kruskal-Wallis	P value
CD4/PD1	35.14 ± 0.43	20.87 ± 0.9	12.59 ± 0.84	12.0 ± 1.33	6700.7	< 0.001c
Post hoc7	1P < 0.001c, 2P < 0.001c, 3P = 0.001b, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD8/PD1	35.57 ± 0.58	23.89 ± 0.81	15.6 ± 0.84	15.0 ± 1.33	5854.15	< 0.001c
Post hoc7	1P < 0.001c, 2P < 0.001c, 3P = 0.007b, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD4/TIGIT	13.77 ± 0.37	8.76 ± 0.46	6.18 ± 0.79	5.6 ± 1.33	1011.91	< 0.001c
Post hoc7	1P < 0.001c, 2P > 0.999, 3P = 0.003b, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD8/TIGIT	17.66 ± 0.38	6.56 ± 0.46	7.6 ± 0.77	7.0 ± 1.32	2088.86	< 0.001c
Post hoc7	1P < 0.001c, 2P < 0.001c, 3P =0.002b, 4P < 0.001c, 5P < 0.001c, 6P =0.043a
CD4/TIM3	14.7 ± 0.34	6.34 ± 0.46	3.6 ± 0.77	3.0 ± 1.33	2169.06	< 0.001c
Post hoc7	1P < 0.001c, 2P > 0.999, 3P = 0.002b, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD8/TIM3	17.14 ± 0.44	8.56 ± 0.46	4.1 ± 0.77	3.5 ± 1.33	2868.84	< 0.001c
Post hoc7	1P < 0.001c, 2P < 00.001c, 3P = 0.002b, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD3	66.12 ± 0.68	67.84 ± 0.83	71.25 ± 0.88	71.15 ± 1.37	339.21	< 0.001c
Post hoc7	1P < 0.001c, 2P < 0.001c, 3P = 0.945, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD4	39.06 ± 0.75	43.95 ± 0.91	47.25 ± 0.88	47.15 ± 1.37	733.67	< 0.001c
Post hoc7	1P < 0.001c, 2P < 0.001c, 3P = 0.95, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
CD8	21.06 ± 0.69	23.98 ± 0.87	24.25 ± 0.88	24.15 ± 1.37	122.07	< 0.001c
Post hoc7	1P < 0.001c, 2P = 0.05, 3P = 0.947, 4P < 0.001c, 5P < 0.001c, 6P = 0.829
CD4/CD8	1.86 ± 0.03	1.83 ± 0.03	1.95 ± 0.03	1.96 ± 0.05	140.79	< 0.001c
Post hoc7	1P = 0.023a, 2P < 0.001c, 3P = 0.852, 4P < 0.001c, 5P < 0.001c, 6P < 0.001c
AFP (ng/mL)	13210 (11008.3-14956.8)	4 (2-6)	6.85 (6.08-7.5)	4.3 (3.08-5.53)	144.208	< 0.001c
Post hoc7	1P < 0.001c, 2P < 0.001c, 3P < 0.001c, 4P < 0.001c, 5P < 0.001c, 6P = 0.883

¹P: Hepatocellular carcinoma vs cirrhosis.

²P: Hepatocellular carcinoma vs hepatitis C virus.

³P: Hepatitis C virus vs control.

⁴P: Hepatocellular carcinoma vs control.

⁵P: Cirrhosis vs control.

⁶P: Cirrhosis vs hepatitis C virus.

⁷Post hoc: Tukey’s test for ANOVA (CD4/programmed death 1, CD8/ programmed death 1, CD4/T cell immunoglobulin and ITIM domain, CD8/T cell immunoglobulin and ITIM domain, CD4/T cell immunoglobulin and mucin domain-containing protein 3, CD8/T cell immunoglobulin and mucin domain-containing protein 3, CD3, CD4, CD8, CD4/CD8).

⁸F: One-way ANOVA test; ANOVA adjusted for Child-Pugh class and age using ANCOVA for hepatocellular carcinoma and cirrhosis groups to control for liver function and demographic confounders; Kruskal-Wallis for alpha-fetoprotein used Dunn’s post hoc test.

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

PD-1: Programmed death 1; TIGIT: T-cell immunoglobulin and ITIM domain; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus.