Single-Cell Proteomics Analysis of Recurrent Low-Grade Serous Ovarian Carcinoma and Associated Brain Metastases

Abstract

Between 2% and 6% of epithelial ovarian cancer (EOC) patients develop brain metastases (brain mets), which are incurable and invariably result in death. This poor outcome is associated with a lack of established guidelines for the detection and treatment of brain mets in EOC patients. In this study, we characterize an unusual case of low-grade serous ovarian carcinoma (LGSOC) that metastasized to the brain. Using a spatially oriented single-cell proteomics platform, we compared sequential biopsies of a primary tumor with a peritoneal recurrence and brain mets. We identified several targetable oncogenic pathways and immunosuppressive mechanisms that are amplified in the brain mets and could be involved in the progression of LGSOC to the brain. Furthermore, we were able to identify cell populations that are shared between the primary tumor and the brain mets, suggesting that cells that have a propensity for metastasis to the brain could be identified early during the course of disease. Taken together, our findings further a path for personalized therapeutic decisions in LGSOC.

Proteomics mining of cancer hallmarks on a single‐cell resolution

“…Cancer metastasis involves a number of dysregulated proteins and pathways (Weiss et al, 2022). Pejovic et al (2022) revealed various targetable carcinogenic pathways and immunosuppressive mechanisms that potentially determined brain metastases of epithelial ovarian cancer via a spatially oriented single‐cell proteomics platform. Notably, the spatially oriented single‐cell proteomics platform also uncovered that in the early stage of brain metastasis, the specific cell subtype has already emerged in the primary tumor.…”