Mallela Venkata Ramana, Rajtmajerová Marie, Ali Esraa, Červenková Lenka, Trailin Andriy, Hošek Petr, Pálek Richard, Daum Ondřej, Liška Václav, Hemminki Kari, Ambrozkiewicz Filip
Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, 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.
Noncoding RNA Res. 2025 Jul 25;15:100-107. doi: 10.1016/j.ncrna.2025.07.006. eCollection 2025 Dec.
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.
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.
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.
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.
肝细胞癌(HCC)是全球第三大致命性癌症。其高死亡率主要归因于晚期诊断。虽然驱动基因的突变,如编码β-连环蛋白(CTNNB1)、肿瘤蛋白p53(TP53)和端粒酶逆转录酶启动子(TERTp)的基因的突变在文献中有充分记载,但作为关键翻译调节因子的微小RNA(miRNA)的失调仍知之甚少。
我们对45例非病毒性HCC患者的配对(肿瘤和非肿瘤相邻组织)样本进行了微阵列miRNA分析。我们对复发时间(TTR))、无病生存期(DFS)和总生存期进行了临床相关性、ROC分析和生存分析。
我们鉴定出23种显著失调的miRNA(p≤0.05,倍数变化≥2)。我们研究了它们的差异表达及其与临床和病理变量的关系。此外,我们发现miRNA-1972可能是一个重要的阳性预后标志物,因为其高水平与更长的TTR和DFS相关。miR-1972、miR-3651和miR-486-5p在受试者工作特征分析中获得了显著阳性结果。
miRNA-1972是非病毒性HCC的一个强有力的预后标志物。其他几种miRNA的失调与病理变量有关,如肿瘤内基质数量微血管侵犯和微结节性。