The proteomes of ovarian cancer ascitic cellular aggregates correlate with their ex vivo platinum sensitivities: a pilot study

The accumulation of malignant ascites in the peritoneal cavity is a hallmark of advanced epithelial ovarian cancer (EOC). This fluid contains three-dimensional multicellular aggregates known as spheroids, which contribute to chemoresistance and are an accessible source of tumour material. However, many studies use spheroids generated from primary cell suspensions to reduce heterogeneity. Here, we compare the proteomes and the response to chemotherapeutics of native spheroids directly collected from ascites to spheroids generated ex vivo . We demonstrate that the chemoresponse of native spheroids correlates with patients’ therapy responses in 4/5 cases. In contrast, all ex vivo- generated spheroids were resistant to carboplatin treatment and did not correlate with the clinical outcome. In addition, proteomics quantified over 6,300 proteins per sample, revealing that the global proteomes of native spheroids cluster according to their carboplatin response. A detailed analysis of the upregulated proteins highlights the potential role of extracellular matrix proteins in regulating chemoresponse. This pilot study suggests key proteins and biological pathways that may facilitate a global proteomics-based screening strategy for personalised EOC treatment. As such, native spheroids have the potential to be used to personalise the treatment of all diseases that cause malignant ascites.