Mass spectrometric detection of candidate protein biomarkers of cancer cachexia in human urine

Abstract

Abstract. Increased membrane permeability and myofibrillar protein breakdown are established features of cancer cachexia. Proteins released from cachectic muscle may be excreted in urine to act as biomarkers of the cachectic process. Onedimensional SDS polyacrylamide gel electrophoresis followed by matrix-assisted laser desorption/ionisation or liquid chromatography tandem mass spectrometry was used to compare the protein content of urine from cachectic (>10% weight loss) (n=8) and weight-stable (n=8) gastro-oesophageal cancer patients and healthy controls (n=8). Plasma creatine kinase concentration was used as a marker of gross muscle breakdown. The number of protein species identified in cachectic samples (median 42; range 28-61; total 199) was greater than that identified in weight-stable cancer (median 15; range 9-28; total 79) and control samples (median 12.5; range 5-18; total 49) (P<0.001). Many of the proteins identified have not been reported previously in the urine of cancer patients. Proteins identified specifically in cachectic samples included muscle (myosin species), cytoskeletal (·-spectrin; nischarin) and microtubule-associated proteins (microtubule-actin crosslinking factor; microtubule-associated protein-1B; bullous pemphigoid antigen 1), whereas immunoglobulin κ-light chain and zinc ·-2 glycoprotein appeared to represent markers of cancer. The presence of myosin in urine (without an increase in plasma creatine kinase) is consistent with a specific loss of myosin as part of the cachectic process. Urinary proteomics using mass spectrometry can identify muscle-specific and non-muscle-specific candidate biomarkers of cancer cachexia.

Biomarkers for Cancer Cachexia: A Mini Review

“…Further investigation is required to find if the level of circulating collagen specifically correlates to muscle wasting in cancer cachexia. Using mass spectrometry, muscle wasting products including myosin species, α-spectrin, nischarin, microtubule-actin crosslinking factor, microtubule-associate protein-1B, and bullous pemphigoid antigen 1 were found in urine samples from cachectic patients [ 82 ]. However, this finding is based on a small cohort of patients and requires analysis in a larger sample size prior to clinical application.…”