Comprehensive proteome analysis of human skeletal muscle in cachexia and sarcopenia: a pilot study
| Autor: | Carolyn A. Greig, H. Alexander Ebhardt, Valentina Tadini, Ruedi Aebersold, Simone Degen, Carsten Jacobi, Alain Schilb, Kenneth C. H. Fearon, Neil Johns |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty business.industry Cancer Skeletal muscle medicine.disease Bioinformatics Cachexia 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Weight loss 030220 oncology & carcinogenesis Physiology (medical) Sarcopenia Myosin medicine Orthopedics and Sports Medicine Tumor necrosis factor alpha medicine.symptom business Wasting |
| Zdroj: | Journal of Cachexia, Sarcopenia and Muscle. 8:567-582 |
| ISSN: | 2190-5991 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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