Association of neuromuscular disjunction with cachexia in patients with gynecological cancers

Abstract

Purpose: The potential contributions of neuromuscular junction (NMJ) degradation to muscle loss in cancer remain poorly understood. We investigated the biomarkers of NMJ loss to muscle decline in patients with gynecological carcinomas. Methods: We recruited women with endometrial (n = 37, 56–73 years old) or ovarian (n = 40, 55–72 years old) carcinomas along with age-matched controls (n = 47, 55–71 years old) controls, divided into two subgroups based on the presence of age-associated muscle loss, termed sarcopenia. We measured plasma c-terminal agrin-fragment-32 (CAF22; biomarker of NMJ loss), neurofilament light chain (NF-L; biomarker of neurodegeneration), handgrip strength (HGS), appendicular skeletal muscle mass index (AMMI), and short physical performance battery (SPPB; marker of physical capacity). Results: Patients with endometrial or ovarian carcinomas exhibits low HGS, AMMI, and SPPB along with higher plasma NF-L levels than in controls (all p < 0.05). We found a modest elevation of plasma CAF22 levels in ovarian but not in endometrial carcinomas. The presence of sarcopenia was associated with further elevation of plasma NF-L but not CAF22 levels. Higher carcinoma stages were associated with higher plasma CAF22 in endometrial carcinoma and higher NF-L levels in both groups of carcinoma patients. Conclusion: Collectively, NMJ degradation may have a modest contribution to muscle loss and sarcopenia in gynecological carcinomas. The strategies to counter muscle loss in carcinomas may target intrinsic changes within skeletal muscle independent of NMJ.

Keywords

• Cancer cachexia
• Neuromuscular junction
• CAF22
• Endometrial cancer
• Ovarian cancer
• Short physical performance battery