AI Article Synopsis

  • Cancer cachexia, characterized by muscle loss in cancer patients, poses a significant challenge due to its unclear causes and lack of early predictive biomarkers, making early intervention crucial.
  • Advanced proteomic techniques were employed to analyze muscle biopsies, identifying distinct molecular changes in cancer cachexia patients compared to healthy individuals and those with age-related muscle loss.
  • This research provides insights into the mechanisms behind cancer-induced muscle wasting and suggests a shift from weight loss as a primary indicator of cachexia to a more accurate protein-based signature.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566647PMC
http://dx.doi.org/10.1002/jcsm.12188DOI Listing

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