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Potential Early Biomarkers for Cancer-Associated Body Weight Loss

New Research Findings, IDC,

Researchers at Helmholtz Zentrum München identified specific fat molecules which affect metabolism during cachexia, a cancer-related energy-wasting syndrome characterized by progressive decrease in muscle and fat tissue mass. These fat molecules may function as early cachexia biomarkers, thereby enabling potential novel developments in cachexia prediction, diagnosis and treatment.

Cancer cachexia is of high clinical relevance, since it negatively affects the quality of life, reduces the efficiency of anti-cancer therapies and ultimately shortens the survival of patients with cancer. Up to date, there is no therapy to reverse the body weight loss associated with cachexia. Despite many advances in cachexia research, the origins of the syndrome are still not fully understood.

Specific lipids in the blood characterize cancer-associated body weight loss

Researchers at the Institute for Diabetes and Cancer at Helmholtz Zentrum München hypothesized that specific fat molecules (lipids), which are known to have a significant impact on metabolic health in diabetes, might also play an important role in cachexia development. In order to investigate this hypothesis, the researchers took advantage of the Lipidyzer platform and teamed up with scientists at the Genome Analysis Center of Helmholtz Zentrum München to perform a broad lipid analysis. Their goal was to identify specific lipid species as markers of cancer cachexia by comparing plasma from different commonly used mouse models of cancer cachexia as well as weight-stable and cachectic cancer patients.

Julia Zuber and Pauline Morigny, who share the first authorship of this study, were surprised by the clear results obtained from numerous different mouse models and patients with cancer. They found a clear discrimination between the lipid profiles under cachexia or weight-stable conditions. Interestingly, the circulating amounts of eight lipid species closely correlated with the percentage of body weight loss (i.e. the severity of the disease in mice and humans). This implies a potential functional role of these eight lipid species in processes contributing to weight loss.

Translational potential

Due to the lack of a single therapy against cachexia, treatment should be initiated as early as possible. Therefore, biomarkers are needed to detect patients at risk to develop cancer cachexia at an early stage. “Our study provides the potential to use the identified lipids as early cachexia biomarkers. Next to diagnosis, it also allows for treatment implications, such as nutritional support measures fighting specific lipid deficiencies occurring during cachexia to counteract the wasting syndrome”, says Dr. Maria Rohm, who led this research together with Dr. Mauricio Berriel Diaz. Additional funds to follow up on this project were recently awarded to Maria Rohm by the European Research Council (ERC).

Morigny, Zuber et al., 2020: <link - extern>High levels of modified ceramides are a defining feature of murine and human cancer cachexia. Journal of Cachexia</link>, Sarcopenia and Muscle, DOI: 10.1002/jcsm.1262