摘要
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.
作者简介
Corresponding author:Alexander Link,MD,PhD,Academic Research,Associate Professor,Doctor,Department of Gastroenterology,Hepatology and Infectious Diseases,Otto-von-Guericke University Magdeburg,Leipziger Street 44,Magdeburg 39120,Germany.alexander.link@med.ovgu.de.Alexander Link 0000-0002-9514-4562;ORCID number:Martin Franck 0000-0001-6889-2955;Cosima Thon 0000-0002-8954-6119;Kerstin Schütte 0000-0002-1724-3733;Peter Malfertheiner 0000-0001-8439-9036。