BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the third deadliest cancer worldwide. Its high mortality is primarily attributed to late-stage diagnosis. While mutations in driver genes, such as those encoding β-catenin (CTNNB1), tumor protein p53 (TP53), and telomerase reverse transcriptase promoter (TERTp) are well-documented in the literature, dysregulation of microRNAs (miRNAs), small non-coding RNAs that serve as crucial translational regulators, remains poorly understood. METHODS: We conducted microRNA profiling by microarrays in 45 paired (tumor and non-tumor adjacent tissue) samples from non-viral HCC patients. We performed clinical correlation, ROC analysis and survival analysis of time to recurrence (TTR), disease-free survival (DFS) and overall survival. RESULTS: We identified 23 significantly dysregulated miRNAs (p ≤ 0.05, fold change ≥2). We investigated their differential expression and its relationship with clinical and pathological variables. Further, we found that miRNA-1972 may serve as an important positive prognostic marker because its high levels were associated with longer TTR and DFS. Significant positive results were obtained in receiver operating characteristic analysis for miR-1972, miR-3651 and miR-486-5p. CONCLUSION: miRNA-1972 is a strong prognostic marker in non-viral HCC. Dysregulation of several other miRNAs relates to pathological variables such as amount of stroma within tumor, microvascular invasion and micronodularity.

Bioptická Laboratoř s r o Mikulášské Nám 4 32600 Pilsen Czech Republic

Department of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 280 69120 Heidelberg Germany

Department of Surgery University Hospital in Pilsen and Faculty of Medicine in Pilsen Charles University Alej Svobody 80 323 00 Pilsen Czech Republic

Laboratory of Cancer Treatment and Tissue Regeneration Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 323 00 Pilsen Czech Republic

Laboratory of Translational Cancer Genomics Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 323 00 Pilsen Czech Republic

Sikl's Institute of Pathology Faculty of Medicine and Teaching Hospital in Plzen Charles University ul Dr E Beneše 13 30599 Pilsen Czech Republic

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