Molecular indicators of hepatocellular carcinoma resistance to Y-90 microspheres revealed through high-throughput screening of cell lines and transcriptomics

Molecular signatures predict prognosis in hepatocellular carcinoma; however, their relevance to Y-90 radioembolization remains unknown. Here, we perform Y-90 microsphere screens in a panel of genetically diverse human HCC cell lines. Ten transcriptomically diverse human HCC cell lines were exposed to 20 MBq of Y-90 glass beads. Normalized AUC values qualified sensitivity. Whole-transcriptome RNA sequencing at baseline and post-treatment underwent differential expression analysis and gene set enrichment analysis. The response of HCC cell lines to Y-90 was heterogeneous, with SK-Hep1 and SNU-449 being the most resistant and PLC/PRF/5 being the most sensitive. Overall design: RNA-seq profiling of genetically diverse human HCC cell lines SK-Hep1, Hep-3B, Hep-G2, MHCC-97H, SNU-449, SNU-423, SNU-475, SNU-387, PLC/PRF/5, and SNU-398 before and after treatment with 20 MBq of Y-90.