Spatial atlas reveals how ovarian clear cell tumors vary from core to edge

A recent study published in Nature Communications has unveiled significant spatial heterogeneity within ovarian clear cell carcinoma (OCCC) tumors, offering new insights into the disease's progression and potential treatment options. Led by Professor Ruby Yun-Ju Huang from National Taiwan University College of Medicine, an interdisciplinary team employed advanced spatial transcriptomics technologies, including GeoMx, Visium, and CosMx, alongside cellular functional validation and chick embryo chorioallantoic membrane (CAM) models to construct the first comprehensive spatial map of OCCC.

The research identified distinct molecular characteristics between cancer cells in the tumor center and those near regions of invasion, necrosis, and hemorrhage. The tumor center cells demonstrated higher oxidative phosphorylation (OXPHOS) activity and epithelial traits, while edge cells exhibited reduced metabolic activity and increased epithelial-mesenchymal transition (EMT) characteristics.

Specifically, the expression of the metabolism-related gene LCN2 was linked to higher OXPHOS activity and epithelial traits in tumor cells. Patients with higher LCN2 expression, coupled with pronounced epithelial features, had a relatively better overall prognosis. The study further revealed that the transcription factor SOX9 regulates LCN2 expression, suggesting a crucial mechanism governing cancer cell state transitions and tumor plasticity.

This finding points towards the SOX9- LCN2 pathway as a potential target for more precise therapeutic strategies in OCCC. The research involved two co-first authors, Lê Trương Thắng and Ducan Yi-Te Wang, both from National Taiwan University, bringing diverse expertise to the project.