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

BACKGROUND: There is ongoing search for new noninvasive biomarkers to improve management of patients with hepatocellular carcinoma (HCC). Studies, mostly from the Asian-Pacific region, demonstrated differential expression of liver-specific microRNA-122 (miR-122) in tissue as well as in sera of patients with hepatitis B virus- and hepatitis C virus-induced HCC. AIM: To evaluate prognostic value of miR-122 in patients with HCC in a European population and determine potential factors related to alteration of miR-122 in sera. METHODS: Patients with confirmed HCC (n = 91) were included in the study over a two-year period. Patients were characterized according to Child-Pugh score, Barcelona clinic liver cancer (BCLC) staging system, etiology of liver disease, laboratory parameters and overall survival. MiR-122 was measured in sera using TaqMan assay normalized to spiked-in cel-miR-39. RESULTS: Serum miR-122 quantity was independent of the Child-Pugh score, the BCLC stage or the underlying etiology. Significant positive correlation was found between miR-122 and alanine aminotransferase (P < 0.0001), aspartate aminotransferase (P = 0.0001), alpha-fetoprotein (AFP) (P = 0.0034) and hemoglobin concentration (P = 0.076). Negative correlation was observed between miR-122 level and creatinine concentration (P = 0.0028). AFP, Child-Pugh score and BCLC staging system were associated with survival differences. In overall cohort low miR-122 in sera was only associated with a trend for a better overall survival without reaching statistical significance. Subgroup analysis revealed that low miR-122 was significantly associated with better prognosis in patients with advanced cirrhosis (Child-Pugh class B/C), advanced tumor stage (BCLC B/C/D) and normal AFP (< 7 ng/mL). CONCLUSION: Our results strongly support the value of miR-122 as potential biomarker of liver injury and probably prognosis. Nevertheless, the value of miR-122 in prediction of prognosis of HCC patients was limited to certain patients' subgroups. Since circulating miR-122 may be influenced by impaired renal function, AFP and hemoglobin concentration, those factors need to be considered while interpreting miR-122 level.