Prognostic value of serum microRNA-122 in hepatocellular carcinoma is dependent on coexisting clinical and laboratory factors

Figure 1 Serum microRNA-122 level in correlation to Child-Pugh score, Barcelona clinic liver cancer stage and underlying etiology. A: Serum microRNA-122 (miR-122) level in relation to Child-Pugh score: No liver cirrhosis (n = 16), class A (n = 45), class B (n = 27), and class C (n = 3); B: Serum miR-122 level in relation to Barcelona clinic liver cancer staging system: Stage A (n = 16), stage B (n = 37), stage C (n = 32), and stage D (n = 6); C: Serum miR-122 level in relation to underlying etiology of the hepatocellular carcinoma: Alcohol abuse (n = 41), viral hepatitis (n = 12), non-alcoholic steatohepatitis (n = 13), hemochromatosis (n = 6), rare or other (n = 19). Kruskal-Wallis test and post-hoc Dunn’s test were used for statistical analysis. LC: Liver cirrhosis; NASH: Non-alcoholic steatohepatitis; BCLC: Barcelona clinic liver cancer.

Figure 2 Relation between serum microRNA-122 level and other laboratory parameters. A: Differences of serum microRNA-122 (miR-122) in relation to alanine aminotransferase (ALAT) [ALAT normal: ≤ 0.58 (w) / 0.83 (m) μmol/Ls, ALAT pathological: > 0.58 (w) / 0.83 (m) μmol/Ls]; B: Differences of serum miR-122 in relation to aspartate aminotransferase (ASAT) [ASAT normal: ≤ 0.58 (w) / 0.83 (m) μmol/Ls, ASAT pathological: > 0.58 (w) / 0.83 (m) μmol/Ls]; C: Differences of serum miR-122 in relation to alpha-fetoprotein (AFP) (AFP normal: AFP < 7 ng/mL, AFP slightly increased: 7 ng/mL ≤ AFP ≤ 400 ng/mL, AFP clearly increased: AFP > 400 ng/mL); D: Differences of serum miR-122 in relation to creatinine [Crea normal: ≤ 84 (w) / 104 (m) µmol/L, Crea pathological: > 84 (w) / 104 (m) µmol/L]; E: Differences of serum miR-122 in relation to hemoglobin [Hb normal: ≥ 7.4 (w) / 8.6 (m) mmol/L, Hb pathological: < 7.4 (w) / 8.6 (m) mmol/L]. Mann-Whitney test, Kruskal-Wallis test and post-hoc Dunn’s test were used for statistical analysis. ^aP < 0.05 and ^bP < 0.01 vs normal group, not significant- not shown. ASAT: Aspartate aminotransferase; ALAT: Alanine aminotransferase; AFP: Alpha-fetoprotein; Crea: creatinine.

Figure 3 Survival analysis in relation to alpha-fetoprotein, Child-Pugh score, Barcelona clinic liver cancer stage and serum microRNA-122 level. A: Survival analysis in hepatocellular carcinoma (HCC) patients in relation to alpha-fetoprotein (AFP) [divided into three groups: patients with regular AFP (< 7 ng/mL, n = 33), patients with slightly (7 ng/mL ≤ AFP ≤ 400 ng/mL, n = 33) and patients with clearly increased AFP (> 400 ng/mL, n = 25)]; B: Survival analysis in HCC patients in relation to Child-Pugh score [divided into three groups: patients without cirrhosis (n = 16), patients with Child-Pugh class A (n = 45), and patients with Child-Pugh class B or C (n = 30), class B and class C were summarized, because only a few patients were in the more severe class (n = 3)]; C: Survival analysis in HCC patients in relation to Barcelona clinic liver cancer (BCLC) staging system [divided into three groups: patients with BCLC A (n = 16), with BCLC B (n = 37), with BCLC C or D (n = 38), BCLC C and BCLC D were summarized, because only a few patients were in the more severe stage (n = 6)]; D: Survival analysis in HCC patients in relation to serum miR-122 level [divided into three groups: < 25^th percentile (n = 22), 25^th-75^th percentile (n = 46), ≥ 75^th percentile (n = 23)]. Nonparametric log-rank test was used for statistical analysis. ^bP < 0.01: AFP normal vs AFP slightly increased vs AFP clearly increased; ^dP < 0.01 No liver cirrhosis vs Child A vs Child B or C; ^fP < 0.01 BCLC A vs BCLC B vs BCLC C or D. BCLC: Barcelona clinic liver cancer; AFP: Alpha-fetoprotein.

Figure 4 Survival analysis of subgroups of patients depending on serum microRNA-122 level. A: Survival analysis in relation to serum miR-122 in all patients [divided into two groups: < 25^th percentile (n = 22), ≥ 25^th percentile (n = 69)]; B: Survival analysis in relation to serum miR-122 in patients with Child-Pugh class B or C [divided into two groups: < 25^th percentile (n = 7), ≥ 25% percentile (n = 23)]; C: Survival analysis in relation to serum miR-122 in patients with Barcelona clinic liver cancer stage B/C/D [divided into two groups: < 25^th percentile (n = 18), ≥ 25^th percentile (n = 57)]; D: Survival analysis in relation to serum miR-122 in patients with normal alpha-fetoprotein (AFP) (AFP < 7 ng/mL) [divided into two groups: < 25^th percentile (n = 8), ≥ 25^th percentile (n = 25)]. Nonparametric log-rank test was used for statistical analysis. P < 0.05 miR-122 < 25^th percentile vs miR-122 ≥ 25^th percentile. BCLC: Barcelona clinic liver cancer; AFP: Alpha-fetoprotein.