Distinct metabolic profiles of ascites in patients with solid tumors

Background Ascites development in patients with cancer is associated with considerable morbidity and mortality, representing an unmet clinical need. The development of targeted treatment strategies was so far hampered by a lack of pathophysiologic insight. Methods Patients with ascites due to solid tumors (n = 35) and non-malignant ascites due to liver cirrhosis (n = 5) were prospectively enrolled. Patients with peritonitis, defined as an absolute neutrophil count > 0.25 G/l in ascites were excluded from analysis. Metabolomic profiling of ascites samples was performed using the MxP Quant 500 kit (Biocrates) and analyzed with MetaboAnalystR v4 and R. Results Among patients with solid tumors, 18 (51.4%) presented with negative tumor cell cytology (paramalignant) and 17 (48.6%) with positive tumor cell cytology (malignant). Tumors originated from the pancreas (42.9%), upper gastrointestinal tract (28.6%), colon (14.3%) or biliary tract (14.3%). Principal component analysis suggested grouping of samples based on presence of tumor cells within the ascites, while non-malignant samples were not associated with a distinct cluster. 110 metabolites showed significantly different levels between malignant and paramalignant samples, as well as six metabolites between malignant and non-malignant samples. Most distinct differences between malignant and paramalignant samples could be observed in higher levels of glutamate, and several lipid species belonging to the ceramide, phosphatidylcholine, cholesterol ester and sphingomyelin classes. No differences were identified between non-malignant and paramalignant samples. Conclusions Metabolic differences in ascites seem to be driven by the presence of tumor cells, indicating diverging underlying pathophysiologic processes. Differentially abundant metabolites were previously associated with alterations in tumor immunity as well as cancer cell proliferation, survival and treatment resistance.