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Detection of Alkaline Sphingomyelinase Activity in Human Stool: Proposed Role as a New Diagnostic and Prognostic Marker of Colorectal Cancer

¹ Department of Drug Science, University G. D'Annunzio, Chieti, Italy; ² Laboratory of Biochemistry, Istituto di Ricovero e Cura a Carattere Scientifico "S. de Bellis"; ³ Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy; and Departments of ⁴ Experimental Medicine and ⁵ Surgical Sciences, University of L'Aquila, L'Aquila, Italy

Requests for reprints: Maria Grazia Cifone, Department of Experimental Medicine, University of L'Aquila Via Vetoio 10, Coppito 2, 67100 L'Aquila, Italy. Phone: 39-862-433503; Fax: 39-862-433523. E-mail: cifone{at}univaq.it

Objectives: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues.

Materials and Methods: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed.

Results: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls.

Conclusion: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms.

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