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 ...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 liverspecific 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.展开更多
BACKGROUND MicroRNAs(miRNAs)have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma(HCC).Specifically,hsa-miR-21-5p(miR-21)is among the most frequently deregulated miRNA in cancer.T...BACKGROUND MicroRNAs(miRNAs)have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma(HCC).Specifically,hsa-miR-21-5p(miR-21)is among the most frequently deregulated miRNA in cancer.The diagnostic and prognostic value of miR-21 has been demonstrated in HCC tissue,mostly in the Asian population.Although the impact of various factors has been recently reported for circulating hsa-miR-122-5p(miR-122),at present only limited knowledge is available for miR-21.AIM To evaluate the value of miR-21 for the assessment of prognosis in HCC patients and to delineate the influence of clinical and preanalytical factors on miR-21 level in sera.METHODS Patients with confirmed HCC from our European cohort with predominantly alcohol-associated liver damage were included in the study.All subjects were characterized according to their clinical and laboratory work-up and overall survival data were obtained.Quantitative real-time polymerase chain reaction was performed for miR-21 and spiked-in cel-miR-39-3p.The results were compared to previously reported miR-122 data.RESULTS Survival of HCC patients was comparable between patients with low and high serum miR-21 concentration.No association was observed between miR-21 level in sera and Child-Pugh score,Barcelona Clinic Liver Cancer staging system,or etiology of HCC/liver disease.Age,gender,or pretreatment had no association with miR-21 level.A positive correlation was observed between miR-21 and aspartate aminotransferase(r=0.2854,P=0.0061),serum miR-122(r=0.2624,P=0.0120),and the International Normalized Ratio(r=0.2065,P=0.0496).Negative correlation of miR-21 with serum creatinine(r=-0.2215,P=0.0348)suggests renal function as a potential influencing factor in miR-21 biogenesis in blood.CONCLUSION The results from this work do not support clinically relevant prognostic value of circulating miR-21 in HCC patients in real-life settings.Following systematic evaluation,we identified renal function and aspartate aminotransferase as potential factors that may affect miR-21 concentration in blood.This knowledge should be considered in future miRNA-based biomarker studies not only for HCC but also for other diseases.展开更多
文摘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 liverspecific 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.
文摘BACKGROUND MicroRNAs(miRNAs)have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma(HCC).Specifically,hsa-miR-21-5p(miR-21)is among the most frequently deregulated miRNA in cancer.The diagnostic and prognostic value of miR-21 has been demonstrated in HCC tissue,mostly in the Asian population.Although the impact of various factors has been recently reported for circulating hsa-miR-122-5p(miR-122),at present only limited knowledge is available for miR-21.AIM To evaluate the value of miR-21 for the assessment of prognosis in HCC patients and to delineate the influence of clinical and preanalytical factors on miR-21 level in sera.METHODS Patients with confirmed HCC from our European cohort with predominantly alcohol-associated liver damage were included in the study.All subjects were characterized according to their clinical and laboratory work-up and overall survival data were obtained.Quantitative real-time polymerase chain reaction was performed for miR-21 and spiked-in cel-miR-39-3p.The results were compared to previously reported miR-122 data.RESULTS Survival of HCC patients was comparable between patients with low and high serum miR-21 concentration.No association was observed between miR-21 level in sera and Child-Pugh score,Barcelona Clinic Liver Cancer staging system,or etiology of HCC/liver disease.Age,gender,or pretreatment had no association with miR-21 level.A positive correlation was observed between miR-21 and aspartate aminotransferase(r=0.2854,P=0.0061),serum miR-122(r=0.2624,P=0.0120),and the International Normalized Ratio(r=0.2065,P=0.0496).Negative correlation of miR-21 with serum creatinine(r=-0.2215,P=0.0348)suggests renal function as a potential influencing factor in miR-21 biogenesis in blood.CONCLUSION The results from this work do not support clinically relevant prognostic value of circulating miR-21 in HCC patients in real-life settings.Following systematic evaluation,we identified renal function and aspartate aminotransferase as potential factors that may affect miR-21 concentration in blood.This knowledge should be considered in future miRNA-based biomarker studies not only for HCC but also for other diseases.
