Gene expression analysis of patient-derived engineered organoid model of thyroid cancer (TC)

Inter-tumor heterogeneity is a major hurdle in thyroid cancer (TC) precision therapy. The use of non-engineered organoids (NEOs), derived from primary tissue, as a potent tool for cancer drug screening is limited by their dependence on inefficient manual procedures. Here, we establish droplet-engineered organoids (DEOs) derived from TC patients using microfluidic technology, which recapitulates histopathology and genomic landscape of parental tumors, and preserve the drug sensitivity differences of patients. Furthermore, we reveal NF-?B pathway as a major mediator of advanced DEOs generation. A NF-?B inhibitor and anti cancer drugs are screened, exhibiting a marked anti-proliferative effect. Together, our study demonstrates a microfluidic-based approach for rapid construction of TC DEOs and investigates the maturation mechanisms, providing an ideal in vitro model and novel insights for the development of therapeutic strategies against thyroid carcinoma. Overall design: RNA-seq profiling of thyroid cancer tissue (TC_M), early-stage thyroid cancer organoids (TCDEO_E) and late-stage thyroid cancer organoids (TCDEO_L)