Circulating miR-21-5p level has limited prognostic value in patients with hepatocellular carcinoma and is influenced by renal function

Figure 1 Serum hsa-miR-21-5p level in correlation to Child-Pugh score, Barcelona Clinic Liver Cancer stage, and underlying etiology. A: Serum hsa-miR-21-5p (miR-21) level and Child-Pugh score: No liver cirrhosis (n = 16), Child-Pugh A (n = 45), Child-Pugh B (n = 27), Child-Pugh C (n = 3), P = 0.7991; B: Serum miR-21 and Barcelona Clinic Liver Cancer (BCLC) staging system: Stage A (n = 16), stage B (n = 37), stage C (n = 32), stage D (n = 6), P = 0.3947; and C: Serum miR-21 and underlying etiology of the hepatocellular carcinoma: Alcohol abuse (n = 41), viral hepatitis (n = 12), non-alcoholic steatohepatitis (NASH) (n = 13), hemochromatosis (n = 6), rare or other (n = 19), P = 0.6331. Kruskal-Wallis test and post-hoc Dunn’s test were used for statistical analysis. MiR-21: Hsa-miR-21-5p.

Figure 2 Correlation analysis of serum hsa-miR-21-5p and common laboratory parameters. Correlation between serum hsa-miR-21-5p and A: Alanine aminotransferase (ALAT); B: Aspartate aminotransferase (ASAT); C: Alpha-fetoprotein (AFP); D: International Normalized Ratio (INR); and E: Creatinine. For 30 patients only laboratory quick value was available and reverse calculation of International Normalized Ratio for values below < 1.5 were performed. Spearman’s correlation coefficient was used for statistical analysis. MiR-21: Hsa-miR-21-5p.

Figure 3 Overall survival analysis in relation to hsa-miR-21-5p level. A: All patients were divided into two groups: (1) Low: < 50^th percentile (n = 47) and (2) High: > 50^th percentile (n = 44), two patients exhibit exactly the median expression of serum hsa-miR-21-5p, that is why, the group division is not exactly symmetric; B: Overall survival analysis in patients with Barcelona Clinic Liver Cancer staging system A + B (divided into two groups: (1) Low: < 50^th percentile [n = 27] and (2) High: > 50^th percentile [n = 26]); C: Survival analysis in patients with Barcelona Clinic Liver Cancer staging system C + D (divided into two groups: (1) Low: < 50^th percentile [n = 20] and (2) High: > 50^th percentile [n = 18]). Nonparametric log-rank test was used for statistical analysis. MiR-21: Hsa-miR-21-5p.

Figure 4 Overall survival analysis in subgroups of patients in relation to hsa-miR-21-5p level. A: Survival analysis in patients with normal creatinine (divided into two groups: (1) Low: < 50^th percentile (n = 33) and (2) High: > 50^th percentile [n = 33]); B: Survival analysis in patients with pathological creatinine (hsa-miR-21-5p [miR-21] low n = 13; miR-21 high n = 12); C: Survival analysis in patients with normal alanine aminotransferase (miR-21 low n = 29; miR-21 high n = 29); D: Survival analysis in patients with pathological alanine aminotransferase (ALAT) (miR-21 low n = 17, miR-21 high n = 16); E: Survival analysis in patients with normal aspartate aminotransferase (ASAT) (miR-21 low n = 15; miR-21 high n = 15); and F: Survival analysis in patients with pathological ASAT (miR-21 low n = 31; miR-21 high n = 30). Nonparametric log-rank test was used for statistical analysis. MiR-21: Hsa-miR-21-5p.

Figure 5 Overall survival analysis in hepatocellular carcinoma patients in relation to serum hsa-miR-21-5p, hsa-miR-122-5p, and alpha-fetoprotein levels. A: Correlation between serum hsa-miR-21-5p (miR-21) and serum hsa-miR-122-5p (miR-122); B: All patients were divided into three groups: Both miR-21 and miR-122 low (50^th percentile, n = 28); one of miR-21 or miR-122 low (50^th percentile, n = 37); both miR-21 and miR-122 high (> 50^th percentile, n = 26); C: Analysis of overall survival of alpha-fetoprotein (AFP) low (n = 24) vs AFP high (n = 23) in patients with low miR-21 levels; and D: Analysis of overall survival of AFP low (n = 22) vs AFP high (n = 22) in patients with high miR-21 levels. Spearman correlation and nonparametric log-rank test were used for statistical analysis. MiR-21: Hsa-miR-21-5p; MiR-122: Hsa-miR-122-5p.