Ascites metabolism differs sharply depending on tumor cells

Fluid accumulating in the abdomen of patients with advanced cancer, known as ascites, carries a metabolic fingerprint that depends on whether tumor cells are actually present in the fluid, according to a prospective study now published as an open access Research article in Cancer & Metabolism. The work, led by Julia M. Berger, Martin Korpan, Maria Koenig, Markus Kleinberger, Katharina Syboeck, Carina Zierfuss, Lynn Gottmann, Vincent Sunder-Plassmann, Georg Kramer, Lorenz Balcar, Fernanda Monedeiro, Denise Schimek, Elisabeth S. Bergen, Thomas Reiberger, Christoph Magnes, Matthias Preusser and Anna S. Berghoff, with Barbara Niederdorfer as senior author, was published on 23 October 2026 as a peer-reviewed, accepted manuscript shared early with a permanent DOI.

The clinical motivation is stark. Ascites development in patients with cancer is associated with considerable morbidity and mortality and represents an unmet clinical need. Efforts to design targeted treatment strategies have so far been hampered by a lack of pathophysiologic insight into what the fluid actually contains and how malignant and non-malignant forms of the condition differ at the molecular level. The new study addresses that gap by systematically profiling the small-molecule chemistry of ascites collected from patients under a defined prospective protocol.

Between the two groups, the researchers enrolled 35 patients whose ascites was caused by solid tumors and 5 patients with non-malignant ascites caused by liver cirrhosis. To keep the analysis clean, patients with peritonitis, defined as an absolute neutrophil count above 0.25 G/l in the ascites fluid, were excluded from analysis.

Within the solid tumor group, the team distinguished two biologically meaningful categories based on cytology. Eighteen patients, or 51.4 percent, had ascites in which no tumor cells could be detected, termed paramalignant ascites, while 17 patients, or 48.6 percent, had malignant ascites with positive tumor cell cytology. The underlying tumors originated from the pancreas in 42.9 percent of cases, the upper gastrointestinal tract in 28.6 percent, the colon in 14.3 percent and the biliary tract in 14.3 percent, giving the cohort a distinctly gastrointestinal and pancreatic character.

When the researchers applied principal component analysis to the metabolomic data, the samples grouped according to the presence of tumor cells within the ascites. Notably, the non-malignant samples from patients with liver cirrhosis were not associated with a distinct cluster of their own, suggesting that the cirrhotic fluid did not form a separate metabolic signature in this small comparison set.

The quantitative differences were substantial. In total, 110 metabolites showed significantly different levels between malignant and paramalignant samples, while six metabolites differed between malignant and non-malignant samples. The most distinct differences between malignant and paramalignant ascites were observed in higher levels of glutamate and in several lipid species belonging to the ceramide, phosphatidylcholine, cholesterol ester and sphingomyelin classes. By contrast, no differences were identified between non-malignant and paramalignant samples, reinforcing the idea that the tumor cells themselves, rather than malignancy in general, drive the metabolic signature.

The authors conclude that metabolic differences in ascites seem to be driven by the presence of tumor cells, indicating diverging underlying pathophysiologic processes between the two forms of cancer-associated ascites.

The study notes that these metabolites have previously been associated with alterations in tumor immunity as well as with cancer cell proliferation, survival and treatment resistance.

Several limitations should be kept in view when interpreting the findings. The non-malignant comparison group comprised only five patients with liver cirrhosis, which limits the statistical power of contrasts involving that group. Because the article is being shared early as an accepted manuscript, the final Version of Record may still undergo further edits.

Even with those caveats, the study provides a concrete, prospectively collected metabolomic map of cancer-associated ascites and a clear signal that tumor cell presence, not merely the diagnosis of cancer, defines the fluid’s chemistry. As the authors frame it, the work points toward diverging pathophysiologic processes behind malignant and paramalignant ascites, a distinction that could guide the development of the targeted treatment strategies that patients with this condition currently lack.

Subject of Research: Metabolomic profiling of ascites in patients with solid tumors and comparison with cirrhosis-related ascites

Article Title: Distinct metabolic profiles of ascites in patients with solid tumors

Article References: Berger, J. M., Korpan, M., Koenig, M., Kleinberger, M., Syboeck, K., Zierfuss, C., Gottmann, L., Sunder-Plassmann, V., Kramer, G., Balcar, L., Monedeiro, F., Schimek, D., Bergen, E. S., Reiberger, T., Magnes, C., Preusser, M., Berghoff, A. S., & Niederdorfer, B. (2026). Distinct metabolic profiles of ascites in patients with solid tumors. Cancer & Metabolism. https://doi.org/10.1186/s40170-026-00463-0

Image Credits: AI Generated

DOI: 10.1186/s40170-026-00463-0

Keywords: ascites, metabolomics, solid tumors, malignant ascites, paramalignant ascites, liver cirrhosis, glutamate, ceramides, phosphatidylcholine, sphingomyelin, tumor immunity, Cancer & Metabolism