Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression

Abstract

Ovarian cancer (OC) patients develop ascites, an accumulation of ascitic fluid in the peritoneal cavity anda sign of tumour dissemination within the peritoneal cavity. This body fluid is under-researched, mainly regarding the ascites formed during tumour progression that have no diagnostic value and, therefore, are discarded. We performed a discovery proteomics study to identify new biomarkers in the ascites supernatant of OC patients. In this preliminary study, we analyzed a small amount of OC ascites to highlight the importance of not discarding such biological material during treatment, which could be valuable for OC management. Our findings reveal that OC malignant ascitic fluid (MAF) displays a proliferative environment that promotes the growth of OC cells that shift the metabolic pathway using alternative sources of nutrients, such as the cholesterol pathway. Also, OC ascites drained from patients during treatment showed an immunosuppressive environment, with up-regulation of proteins from the signaling pathways of IL-4 and IL-13 and down-regulation from the MHC-II. This preliminary study pinpointed a new protein (Transmembrane Protein 132A) in the OC context that deserves to be better explored in a more extensive cohort of patients' samples. The proteomic profile of MAF from OC patients provides a unique insight into the metabolic kinetics of cancer cells during disease progression, and this information can be used to develop more effective treatment strategies.

Keywords: High-grade serous carcinoma; Malignant ascitic fluid; Metabolic pathways; Proteomics; Tumor microenvironment.

Graphical abstract

Fig. 1

Pipeline used to select proteins that are differentially expressed in supernatant of ascitic fluid samples. MAF – malignant ascitic fluid.

Fig. 2

Summary of the pro-tumoral and anti-tumoral relevant proteins (n = 18) present in all MAF samples of OC patients. Proteins described as pro-tumoral (+), anti-tumoral (−); and promoters or suppressors of tumorigenesis according to the tumor context (±).

Fig. 3

Volcano plot representing the variation of proteins from different pathways comparing MAF during treatment vs naïve MAF samples. The top 5 pathways downregulated (green box) and up-regulated (red box) are also described in the volcano plot. These enrichment data were obtained from Proteome Discoverer 2.5.0.400 Software by Gene ontology enrichment, based on the total number of proteins identified (n = 1161). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Heatmap of proteins abundances related to cholesterol pathway, found in naïve and during treatment MAF samples. Data obtained from Proteome Discoverer 2.5.0.400 Software. Protein abundance was calculated from the sum of all unique normalized peptide ion abundances for a specific protein on each run.