Kah Janine, Staffeldt Lisa, Volz Tassilo, Schulze Kornelius, Heumann Asmus, Rövenstrunk Götz, Goebel Meike, Peine Sven, Dandri Maura, Lüth Stefan
Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany.
Viruses. 2025 Apr 30;17(5):653. doi: 10.3390/v17050653.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. HCC is characterized by high heterogeneity and, subsequently, adaptation by developing resistance to current treatments. Applying individualized models is crucial to understanding the potential of approved therapies. Therefore, we classify a primary-like cell line derived from the core region of an HCC with underlying HIV-HCV co-infection employing deep analysis on the pathway regulation level.
We employed DEG analysis, followed by pathway analysis, to characterize the preservation level of the LC4 cells and the level of adoption. Next, we classify the new model for HCC research by employing healthy donor samples, commonly used HCC cell lines, and global RNAseq datasets.
LC4 cells reflect the characteristics of the parental cancer region, including immunosuppression and metabolic reprogramming, characterized by the downregulation of drug-metabolizing enzymes compared to healthy individuals, indicating a transition to alternate metabolic pathways. Moreover, we identified specific biomarkers equally regulated in the parental tissue, in global datasets of the same entities as well as in LC4 cells.
We classified LC4 cells as an individual immunosuppressive and highly progressive primary-like HCC cell line. LC4 cells are applicable as a model for preclinical drug testing, minimizing the lack of preclinical models in HCV-HIV-induced HCC research.
肝细胞癌(HCC)是癌症相关死亡的主要原因之一。HCC具有高度异质性,随后会通过对当前治疗产生耐药性来实现适应。应用个体化模型对于理解获批疗法的潜力至关重要。因此,我们通过对通路调控水平进行深入分析,对源自合并HIV-HCV感染的HCC核心区域的类原代细胞系进行分类。
我们采用差异基因表达(DEG)分析,随后进行通路分析,以表征LC4细胞的保留水平和采用水平。接下来,我们通过使用健康供体样本、常用的HCC细胞系和全球RNA测序数据集,对HCC研究的新模型进行分类。
LC4细胞反映了亲本癌区域的特征,包括免疫抑制和代谢重编程,与健康个体相比,其特征在于药物代谢酶的下调,表明向替代代谢途径的转变。此外,我们在亲本组织、相同实体的全球数据集中以及LC4细胞中鉴定出了受到同等调控的特定生物标志物。
我们将LC4细胞分类为一种个体免疫抑制且高度进展性的类原代HCC细胞系。LC4细胞可作为临床前药物测试的模型,最大限度地减少HCV-HIV诱导的HCC研究中临床前模型的缺乏。