Prognostic Significance of Adiponectin Levels

Background: Circulating adiponectin levels are inversely correlated with the risk of colorectal cancer (CRC). This study was designed to evaluate the association between adiponectin levels and the clinicopathological variables of CRC and to analyze the possible prognostic value of adiponectin in predicting relapse-free survival. Patients and Methods: Baseline adiponectin and serum tumor markers were analyzed in 60 patients with non-metastatic CRC followed-up from time of surgery for at least three years or until relapse. Results: The median adiponectin levels were lower in CRC patients (8.3 Ìg/ml) than controls (13.1 Ìg/ml, p<0.001). Moreover, median adiponectin concentration gradually decreased with increase in tumor stage. Low pre-surgical adiponectin levels were found in 52% of the relapsing patients compared to 26% (p=0.037) of the non-relapsing patients. Logistic regression analysis demonstrated that stage of disease (OR (odds ratio)=15.9, p<0.01) and low adiponectin levels (OR=4.66, p<0.05) were independent predictors of recurrent disease. Conclusion: Low serum adiponectin might represent an adjunctive tool in risk prediction for CRC recurrence. The associations between excess weight, obesity and cancer, as well as the biological mechanisms contributing to these associations, are an evolving and very active area of research. It is generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and cancer. Indeed, recent studies have indicated that some adipokines may significantly influence the growth and proliferation of tumor stroma and the malignant cells within (1). Among them, adiponectin is perhaps the most interesting and promising for the clinician, since it has a profound protective effect on the pathogenesis of obesity-related disorders (2). Adiponectin is a 30-kDa protein hormone and cytokine secreted mainly by adipocytes, structurally related to the collagen superfamily and sharing homologies with collagens, complement factors and tumor necrosis factor-· (TNF-·) (3-6). Epidemiological studies have suggested that circulating adiponectin levels are inversely correlated with the risk of colorectal cancer (CRC) associated with obesity and insulin resistance (7, 8). More recently, a case-control study has demonstrated that men in the highest adiponectin quintile had an approximately 60% reduced risk of colorectal cancer compared to those in the lowest quintile, the association being independent of body mass index (BMI), waist circumference, waist-to-hip ratio and physical activity (9). Moreover, decreased concentrations of plasma adiponectin have been associated with the development of colon adenomas in Japanese patients (10). In particular, significant associations were found between decreased adiponectin levels and the number or size of tumors and histological progression from tubular to tubulovillous/villous adenomas (10). Several mechanisms have been proposed that may link adiponectin to carcinogenesis, such as indirect effects through altering hormone and cytokine levels or direct effects through altering signal pathways involved in cell growth and proliferation (11). Furthermore, experimental 483 Correspondence to: Patrizia Ferroni, MD, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele, Via della Pisana 235, 00163, Rome, Italy. Tel: +39 (06) 66130425, Fax: +39 (06) 66130407, e-mail: [email protected]