Cancer Research Group-School of Life Health and Chemical Sciences, The Open University, Milton Keynes, United Kingdom.
School of Life Sciences, University of Sussex, Brighton, United Kingdom.
PLoS One. 2024 Apr 18;19(4):e0296198. doi: 10.1371/journal.pone.0296198. eCollection 2024.
Robust prognostic and predictive factors for hepatocellular carcinoma, a leading cause of cancer-related deaths worldwide, have not yet been identified. Previous studies have identified potential HCC determinants such as genetic mutations, epigenetic alterations, and pathway dysregulation. However, the clinical significance of these molecular alterations remains elusive. MicroRNAs are major regulators of protein expression. MiRNA functions are frequently altered in cancer. In this study, we aimed to explore the prognostic value of differentially expressed miRNAs in HCC, to elucidate their associated pathways and their impact on treatment response. To this aim, bioinformatics techniques and clinical dataset analyses were employed to identify differentially expressed miRNAs in HCC compared to normal hepatic tissue. We validated known associations and identified a novel miRNA signature with potential prognostic significance. Our comprehensive analysis identified new miRNA-targeted pathways and showed that some of these protein coding genes predict HCC patients' response to the tyrosine kinase inhibitor sorafenib.
在全球范围内,肝癌是导致癌症相关死亡的主要原因,但尚未确定其强有力的预后和预测因素。先前的研究已经确定了肝癌的一些潜在决定因素,如基因突变、表观遗传改变和途径失调。然而,这些分子改变的临床意义仍不清楚。microRNAs 是蛋白质表达的主要调节因子。miRNA 的功能在癌症中经常发生改变。在这项研究中,我们旨在探索差异表达的 miRNA 在 HCC 中的预后价值,阐明它们相关的途径及其对治疗反应的影响。为此,我们采用了生物信息学技术和临床数据集分析,以确定 HCC 与正常肝组织相比差异表达的 miRNA。我们验证了已知的关联,并确定了一个具有潜在预后意义的新 miRNA 特征。我们的综合分析确定了新的 miRNA 靶向途径,并表明其中一些蛋白质编码基因可以预测 HCC 患者对酪氨酸激酶抑制剂索拉非尼的反应。