Spatial transcriptional mapping reveals the molecular characteristics of juxtaglomerular cell tumors

Aside from renin expression, little is known about the molecular markers or signaling pathways involved in the pathogenesis of Juxtaglomerular Cell Tumors (JGCTs). This study aimed to elucidate the molecular characteristics underlying JGCTs.

An 8-year-old girl diagnosed with JGCT underwent laparoscopic partial nephrectomy. Paraffin-embedded tumor tissues were obtained for Spatial Transcriptomic sequencing (STs). The publicly available TCGA database was used to compare the gene expression profiles with those from STs.

The patient presented with typical clinical manifestations of JGCTs. Spatial transcriptomic analysis revealed that juxtaglomerular cells were surrounded by dendritic, endothelial, mast cells, and luminal cells. High expression of REN, KISS1, NOTCH3, CD34, VIM, and GATA3 was detected in JGCT tissues. REN expression was positively correlated with KISS1 expression both in JGCTs and other tumor types, including THYM, THCA, TGCT, and KIRP. In tumor samples, high REN expression was associated with poorer survival outcomes in THYM, KIRP, BRCA-LumA, and ACC. Co-expression network analysis indicated that REN, KISS1, and PPARG regulate endocrine signaling pathways.

Spatial transcriptomics revealed that high KISS1 expression plays a key role in JGCT development. In addition, the PPARG, NOTCH, and PDGFB pathways were identified as potential regulators of renin secretion.