Cell-cycle reactivation and hepatocyte identity loss in hepatocellular carcinoma: Transcriptomic hallmarks and...

Hepatocellular carcinoma (HCC) is molecularly diverse, but repeated transcriptomic surveys point to a useful recurring contrast: Cell-cycle and DNA-replication programs become prominent while differentiated hepatocyte transport, as well as metabolic and innate-defense functions decline. In the present study, this paired change was used as a practical lens for reading HCC transcriptomes. Rather than treating individual proliferation-, transporter- or metabolism-related genes as isolated markers, the review asks what cellular state these modules represent and what evidence is needed before they are discussed as mechanisms or therapeutic vulnerabilities. The present review outlines how proliferation-identity imbalance can guide model choice, RT-qPCR or RNA-seq panels, protein and pathway readouts and pharmacological testing. The current review also includes a worked example showing how a published HCC transcriptomic signal can be interpreted through this framework. The framework is deliberately conservative: Transcriptomic modules can nominate states and experiments, but they do not by themselves establish target dependency, mechanisms or therapeutic efficacy.