Exploring drug resistance via intercellular crosstalk using spatial transcriptomics in high-grade serous ovarian...

Poly(ADP-ribose) polymerase inhibitors (PARPis) have improved the prognosis of patients with high-grade serous ovarian carcinoma (HGSOC). However, PARPis are not effective for all HGSOC patients. Spatial transcriptomics is a powerful tool for characterizing the tumor microenvironment. We used Visium to analyze eight tumor samples from HGSOC patients with clinical information on PARPi sensitivity. Two complementary analyses were performed: an integrated analysis across all samples, without considering spatial information, and an analysis with spatial information within each sample. Both approaches indicated that midkine (MDK) signaling is involved in PARPi resistance. Furthermore, we identified receptors that enhance MDK signaling in cancer cells. To assess the generalizability of this finding, we deconvolved bulk RNA-sequencing data using single-cell RNA-sequencing data as a reference to examine the relationship between receptor expression levels and overall survival (OS). This analysis revealed that high SDC4 expression in cancer cells is associated with poor OS in HGSOC patients.