Body composition and lung cancer-associated cachexia in TRACERx

Area of Science:

• Oncology
• Metabolism
• Genomics

Background:

• Cancer-associated cachexia (CAC) is a debilitating condition prevalent in non-small cell lung cancer (NSCLC).
• CAC significantly contributes to patient morbidity and mortality, characterized by adverse changes in body composition and weight.
• Understanding the biological underpinnings of CAC is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To investigate the association between body composition, body weight, and survival in NSCLC patients.
• To identify biological processes and mediators contributing to the development of CAC.
• To explore the genomic and transcriptomic profiles of tumors in patients with CAC.

Main Methods:

• Computed tomography (CT)-based body composition analysis in the TRACERx and Boston Lung Cancer Study cohorts.
• Genomic and transcriptomic profiling of primary NSCLC tumors.
• Proteomic analysis of circulating mediators in a subset of patients.

Main Results:

• Reduced skeletal muscle or adipose tissue area at diagnosis was linked to significantly shorter lung cancer-specific and overall survival.
• Patients with CAC exhibited distinct tumor genomic and transcriptomic profiles, enriched in inflammatory and epithelial-mesenchymal transitional pathways.
• Circulating GDF15 was significantly associated with body weight and tissue mass loss in patients with CAC.

Conclusions:

• Body composition is a critical prognostic factor in NSCLC, with low muscle and fat mass indicating poor survival.
• CAC development is associated with specific tumor molecular alterations, including inflammatory signaling.
• GDF15 emerges as a potential therapeutic target for managing CAC in NSCLC.