187P - Single-cell RNA sequencing elucidates the role of intercommunication between epithelial cells, immune cells, and fibroblasts in high-grade serous ovarian cancer

Background

The tumour microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) is a complex ecosystem that facilitates ovarian cancer progression. However, further investigation is required to elucidate the precise role of the TME.

Methods

In this study, single-cell RNA sequencing was employed to profile the TME in freshly collected HGSOC samples, comprising two normal ovarian cortex samples and six HGSOC samples.

Results

A total of 55,430 single cells obtained from ovarian and HGSOC tissues were subjected to single-cell RNA sequencing (scRNA-seq). The cells were divided into seven clusters, comprising B cells, T and NK cells, myeloid cells, endothelial cells, fibroblasts, epithelial cells and mast cells. The proportion of B cells, myeloid cells, mast cells and T & NK cells was greater in HGSOC samples than in ovary cortex samples, whereas the percentage of epithelial cells was lower in the former. The analysis of intercommunication of epithelial cells with other cell clusters indicated that the interactions between epithelial cells and fibroblast cells, T & NK cells, B cells as well as myeloid cells were enhanced in in HGSOC samples comparing ovary cortex samples. Additionally, we identified a subcluster of epithelial cells (E7) and a subcluster of fibroblast cells (F7) that were implicated in tumour formation. Finally, we examined the intercommunication between E7 and F7. One of the most significant ligand-receptor signals identified was THBS2-CD74.

Conclusions

The results clearly demonstrated an increase in immune cell percentage in ovarian cancer tissue. Malignant cell clusters, designated as fibroblast cells F7 and epithelial cells E7, were also identified. Among the interactions between F7 and E7, the THBS2-CD74 signal emerged as a crucial factor in the tumourigenesis of HGSOC.

Legal entity responsible for the study

Beijing Obstetrics and Gynecology, Capital Medical University.

Funding

National Natural Science Foundation of China (No. 82373397), the Capital’s Funds for Health Improvement and Research (No. 2022-2-2116), Beijing Municipal Administration of Hospitals Incubating Program (No.PX2022057) and Beijing Obstetrics and Gynecology Hospital, Capital Medical University (No. FCYY201915).

Disclosure

All authors have declared no conflicts of interest.