GSE175716
Activation of FcRn mediates a primary resistance response to sorafenib in hepatocellular carcinoma by single-cell RNA sequencing
Sorafenib is the first-line therapeutic option for advanced hepatocellular carcinoma (HCC). Many patients exhibit a primary resistance response after initial treatment. In previous studies, compared to acquired resistance, the mechanism of primary resistance is unclear. The present study aimed to evaluate the response of patient samples to sorafenib by patient-derived xenograft (PDX) models, and the difference between the sorafenib primary resistance group and the sorafenib sensitive group was analyzed at the single-cell level using single-cell sequencing technology. A special cell cluster may be differentiated by the liver bud hepatic cells, and the JUN transcription factors in this cell cluster were highly activated. The ALB is secreted by other cell clusters, and the cluster stimulates FcRn complex receptor to activate the HIF pathway and cell proliferation, resulting in poor response to sorafenib. These findings are validated by both cell communication analysis and experiments. Thus, the current studies provided a novel approach for the treatment of sorafenib-resistant HCC. Overall design: Comparison of single-cell sequencing between sorafenib primary resistance group and sorafenib sensitive group