Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression

• Published in: Biochemistry and biophysics reports Vol. 39; p. 101755
• Main Authors: Almeida-Nunes, Diana Luísa, Nunes, Mariana, Osório, Hugo, Ferreira, Verónica, Lobo, Cláudia, Monteiro, Paula, Abreu, Miguel Henriques, Bartosch, Carla, Silvestre, Ricardo, Dinis-Oliveira, Ricardo Jorge, Ricardo, Sara
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024; Elsevier
• Subjects: High-grade serous carcinoma; Malignant ascitic fluid; Metabolic pathways; Proteomics; Tumor microenvironment; Metabolic pathways; Tumor microenvironment; Proteomics; High-grade serous carcinoma; Malignant ascitic fluid
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2024.101755

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. Occurrence of malignant ascitic fluid (MAF) during ovarian cancer (OC) progression. In this study, we analyzed the supernatant of MAF samples drained at the time of diagnosis (naïve) and during carboplatin and paclitaxel chemotherapy. These samples were analyzed by liquid chromatography-mass spectrometry (LC/MS) and scrutinized by Proteome Discoverer 2.5.0.400 Software. Our findings evidenced a shift in the proteomic profile of MAF during disease progression. Figure created in Bionrender.com. LC/MS - liquid chromatography-mass spectrometry; APOC2 - Apolipoprotein C-II; UBA1 - Ubiquitin-like modifier-activating enzyme 1. [Display omitted] •The proteomic profile of ascites is a unique opportunity to track the progression of cancer cells.•Cholesterol pathway is increased in ascites during chemotherapy.•Chemotherapy increases IL-4 and IL-13 pathways and decreases MHC-II in ascites.•Ascites proteomics revealed the presence of TMEM132A protein in the context of ovarian cancer.