Journal Article Ppublish 3 citations
PubMed: 39299512 DOI: 10.1016/j.metabol.2024.156034
Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics.
Metabolism 161:156034
Authors: Na Sun, Tanja Krauss, Claudine Seeliger, Thomas Kunzke, Barbara Stöckl, Annette Feuchtinger, Chaoyang Zhang, Andreas Voss, Simone Heisz, Olga Prokopchuk, Marc E Martignoni, Klaus-Peter Janssen, Melina Claussnitzer, Hans Hauner, Axel Walch
Affiliations
- Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
- Else Kröner Fresenius Center for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany.
- Else Kröner Fresenius Center for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany; ZIEL Institute for Food and Health, Technical University of Munich, Freising-Weihenstephan, Germany.
- Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany; Else Kröner Fresenius Center for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany.
- Department of Surgery, Klinikum rechts der Isar, University Hospital of the Technical University of Munich, Munich, Germany.
- The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Institute of Nutritional Science, University of Hohenheim, 70599 Stuttgart, Germany; Department of Medicine, Harvard Medical School, Boston, MA, USA.
- Else Kröner Fresenius Center for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany; ZIEL Institute for Food and Health, Technical University of Munich, Freising-Weihenstephan, Germany; Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.
- Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
Abstract
BACKGROUND
Cancer cachexia (CCx) presents a multifaceted challenge characterized by negative protein and energy balance and systemic inflammatory response activation. While previous CCx studies predominantly focused on mouse models or human body fluids, there's an unmet need to elucidate the molecular inter-organ cross-talk underlying the pathophysiology of human CCx.
METHODS
Spatial metabolomics were conducted on liver, skeletal muscle, subcutaneous and visceral adipose tissue, and serum from cachectic and control cancer patients. Organ-wise comparisons were performed using component, pathway enrichment and correlation network analyses. Inter-organ correlations in CCx altered pathways were assessed using Circos. Machine learning on tissues and serum established classifiers as potential diagnostic biomarkers for CCx.
RESULTS
Distinct metabolic pathway alteration was detected in CCx, with adipose tissues and liver displaying the most significant (P ≤ 0.05) metabolic disturbances. CCx patients exhibited increased metabolic activity in visceral and subcutaneous adipose tissues and liver, contrasting with decreased activity in muscle and serum compared to control patients. Carbohydrate, lipid, amino acid, and vitamin metabolism emerged as highly interacting pathways across different organ systems in CCx. Muscle tissue showed decreased (P ≤ 0.001) energy charge in CCx patients, while liver and adipose tissues displayed increased energy charge (P ≤ 0.001). We stratified CCx patients by severity and metabolic changes, finding that visceral adipose tissue is most affected, especially in cases of severe cachexia. Morphometric analysis showed smaller (P ≤ 0.05) adipocyte size in visceral adipose tissue, indicating catabolic processes. We developed tissue-based classifiers for cancer cachexia specific to individual organs, facilitating the transfer of patient serum as minimally invasive diagnostic markers of CCx in the constitution of the organs.
CONCLUSIONS
These findings support the concept of CCx as a multi-organ syndrome with diverse metabolic alterations, providing insights into the pathophysiology and organ cross-talk of human CCx. This study pioneers spatial metabolomics for CCx, demonstrating the feasibility of distinguishing cachexia status at the organ level using serum.
MeSH
Muscles, Serum, Neoplasms, Multiple Chronic Conditions, Liver, Metabolomics, Tissues, Cachexia, Adipose Tissue, Cancer-Associated Cachexia