Skeletal Muscle Alterations and Functional Repercussions 2 in Patients with Colorectal Cancer-associated Cachexia

Abstract

Cancer cachexia causes skeletal muscle wasting and metabolic dysfunction, worsening clinical outcomes in colorectal cancer (CRC). This study examines microscopic and macroscopic skeletal muscle fiber characteristics, and muscle volume in cachectic and non-cachectic CRC patients compared to healthy controls (HCs), and explores how these factors relate to physical performance. In total, 12 cachectic CRC patients, 25 non-cachectic CRC patients, and 25 HCs were included. Cachexia was determined by weight loss and Cachexia Staging Score. Biopsies from the vastus lateralis and erector spinae muscles were analyzed using immunohistochemistry for muscle fiber type cross-sectional area (CSA) and distribution, myonuclear content, and capillary density. Muscle volume was assessed using three-dimensional ultrasound, and CSA and density by computerized tomography scans. Physical function was evaluated with the Short Physical Performance Battery test, handgrip strength, and the Physical Activity Scale for Individuals with Physical Disabilities. Quality of life was assessed using the 36-item Short Form Survey. Cachectic CRC patients showed reduced type II muscle fiber cross-sectional area in the vastus lateralis compared to HCs and non-cachectic CRC patients. Non-cachectic CRC patients exhibited a slow-to-fast muscle fiber shift compared to HCs. Myonuclear content was lower in both cancer groups. Muscle volume and density were reduced in cachectic CRC patients. Positive correlations were found between microscopic and macroscopic skeletal muscle characteristics, muscle strength, physical performance, and quality of life, respectively. CRC patients, especially those with cachexia, showed type II muscle fiber atrophy, reduced myonuclear content, and impaired physical function, emphasizing the need for targeted prehabilitation interventions.