Vitamin D Receptor Isoform VDRA Suppresses Hepatocellular Tumorigenesis by Restricting YAP Nuclear Localization
To further elucidate the impact of VDRA on HCC proliferation, we established organoid cultures using residual tumor tissues obtained from HCC patients during surgical resection. Importantly, these cultured organoids consistently retained pathological features and markers closely resembling those of the corresponding primary tumors . Subsequently, we performed transcriptome sequencing and whole-exome sequencing (WES) on both organoids and their corresponding HCC tissues. Transcriptomic profiling demonstrated a strong correlation in gene expression between organoids and primary tumors, accompanied by minimal overall expression variability. WES analysis further revealed that 63.5% of the somatic mutations identified in primary tumors were retained in the matched organoids . In addition, organoids and primary tumors exhibited a highly concordant mutational spectrum as well as similar enrichment patterns of signaling pathways influenced by these mutated genes. Collectively, these results indicate that the established organoid model faithfully preserves the genetic landscape of the primary tumors, thereby providing a robust and reliable platform for subsequent functional investigations.