Background: Cancer cachexia (cancer-induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs. age-related sarcopenia are a challenge. However, the ability to distinguish between them is critical for early intervention, and simple measures of body weight may not be sufficiently sensitive to detect cachexia early.
Methods: We used a range of omics approaches: (i) undepleted proteome was quantified using advanced high mass accuracy mass spectrometers in SWATH-MS acquisition mode; (ii) phospho epitopes were quantified using protein arrays; and (iii) morphology was assessed using fluorescent microscopy.
Results: We quantified the soluble proteome of muscle biopsies from cancer cachexia patients and compared them with cohorts of cancer patients and healthy individuals with and without age-related muscle loss (aka age-related sarcopenia). Comparing the proteomes of these cohorts, we quantified changes in muscle contractile myosins and energy metabolism allowing for a clear identification of cachexia patients. In an in vitro time lapse experiment, we mimicked cancer cachexia and identified signal transduction pathways governing cell fusion to play a pivotal role in preventing muscle regeneration.
Conclusions: The work presented here lays the foundation for further understanding of muscle wasting diseases and holds the promise of overcoming ambiguous weight loss as a measure for defining cachexia to be replaced by a precise protein signature.
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http://dx.doi.org/10.1002/jcsm.12188 | DOI Listing |
Nat Rev Cancer
January 2025
Weizmann Institute of Science, Rehovot, Israel.
Metabolic reprogramming of cancer cells and the tumour microenvironment are pivotal characteristics of cancers, and studying these processes offer insights and avenues for cancer diagnostics and therapeutics. Recent advancements have underscored the impact of host systemic features, termed macroenvironment, on facilitating cancer progression. During tumorigenesis, these inherent features of the host, such as germline genetics, immune profile and the metabolic status, influence how the body responds to cancer.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Background: Cachexia is a frequent companion of chronic diseases and a well-established predictor of poor patient performance and outcome. Since cachexia as a discharge diagnosis is not much investigated, we aimed to investigate prevalence of cachexia in hospitalised patients and their outcome.
Methods: We conducted a retrospective analysis of the National Hospital Health Care Statistics Database using the 10th revision of the International Classification of Diseases codes.
Cureus
January 2025
General Surgery, Sunshine Coast University Hospital, Birtinya, AUS.
Background Sarcopenia is the progressive and generalized loss of skeletal muscle and its associated function. Whilst it is typically associated with advanced age, it is also prevalent in patients with chronic diseases including cancer. Patients with esophageal cancer are at high risk of developing malnutrition and sarcopenia due to impaired oral intake, the effects of neoadjuvant treatment, and cancer-related cachexia.
View Article and Find Full Text PDFTumors can exert a far-reaching influence on the body, triggering systemic responses that contribute to debilitating conditions like cancer cachexia. To characterize the mechanisms underlying tumor-host interactions, we utilized a BioID-based proximity labeling method to identify proteins secreted by Yki adult gut tumors into the bloodstream/hemolymph. Among the major proteins identified are coagulation and immune-responsive factors that contribute to the systemic wasting phenotypes associated with Yki tumors.
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