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1 Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, 00168 Rome; 2 Dipartimento di Medicina Clinica, Università 'La Sapienza,' Rome; 3 Dipartimento di Medicina ed Oncologia Sperimentale, Unversità di Torino, Torino; 5 Centro Consiglio Nazionale delle Ricerca di Immunogenetica ed Oncologia Sperimentale, Torino, Italy; and 4 Departament de Bioquimica y Biologia, Universitat de Barcelona, Barcelona, Spain
The intramuscular ATP-dependent ubiquitin (Ub)-proteasome proteolytic system is hyperactivated in experimental cancer cachexia. The present study aimed at verifying whether the expression of the muscle Ub mRNA is altered in patients with cancer. Total muscle RNA was extracted using the guanidinium isothiocyanate/phenol/chloroform method from rectus abdominis biopsies obtained intraoperatively from 20 gastric cancer (GC) patients and 10 subjects with benign abdominal diseases (CON) undergoing surgery. Ub mRNA levels were measured by northern blot analysis. Serum soluble tumor necrosis factor receptor (sTNFR) was measured by ELISA. Ub mRNA levels (arbitrary units, means ± SD) were 2,345 ± 195 in GC and 1,162 ± 132 in CON (P = 0.0005). Ub mRNA levels directly correlated with disease stage (r = 0.608, P = 0.005), being 1,945 ± 786 in stages I and II, 2,480 ± 650 in stage III, and 3,799 ± 66 in stage IV. Ub mRNA and sTNFR did not correlate with age and nutritional parameters. This study confirms experimental data indicating an overexpression of muscle Ub mRNA in cancer cachexia. Lack of correlation with nutritional status suggests that Ub activation in human cancer is an early feature that precedes any clinical sign of cachexia.
cachexia; protein breakdown; proteolytic pathways
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