Emerging markers of cachexia predict survival in cancer patients

Abstract

Background: Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated.

Methods: 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months.

Results: Ghrelin levels were significantly higher in cancer patients than in healthy subjects (573.31 ± 130 vs 320.20 ± 66.48 ng/ml, p < 0.0001), while obestatin (17.42 ± 7.12 vs 24.89 ± 5.54 ng/ml, p < 0.0001) and leptin (38.4 ± 21.2 vs 76.28 ± 17.48 ng/ml, p < 0.0001) values were lower. At ROC analyses the diagnostic profile of ghrelin (AUC 0.962; sensitivity 83%; specificity 98%), obestatin (AUC 0.798; sensitivity 74.5%; specificity 81.5%) and leptin (AUC 0.828; sensitivity 79%; specificity 73%) was superior to that of albumin (AUC 0.547; sensitivity 63%, specificity 69.4%) for detecting cachexia among cancer patients. On Cox multivariate analyses ghrelin (HR 1.02; 95% CI 1.01 - 1.03; p < 0.0001) and leptin (HR 0.94; 95% CI 0.92 - 0.96; p < 0.0001) were significant predictors of death even after correction for other known risk factors such as presence of metastasis and chronic kidney disease.

Conclusion: Ghrelin and leptin are promising biomarkers to diagnose cachexia and to predict survival in cancer patients.

Figure 1

Univariate relationships between ghrelin & obestatin and ghrelin & leptin.

Figure 2

Receiver operating characteristics (ROC) curves. ROC curves of ghrelin, leptin, obestatin and albumin in oncological subjects with cachexia.

Figure 3

Kaplan–Meier all-cause mortality curves. A Kaplan-Meier survival curves of end-point (mortality during a median follow-up period of 18 months) in patients with ghrelin, leptin, albumin and obestatin levels above and below the optimal receiver operating characteristics cut-off level. Patients with ghrelin >663 ng/ml showed a significantly faster progression to endpoint (log-rank (χ²) 5.02; p = 0.02) B Association of ghrelin, leptin or albumin to provide the best predictive model of mortality. Patients with high levels of ghrelin and low leptin levels were characterized by the worst outcome (log-rank (χ²) 8.02; p = 0.004). Patients with low levels of ghrelin and high levels of albumin instead had the best profile, although there were no statistically significant differences if compared with patients with low levels of ghrelin and high levels.

Figure 4

Cox proportional hazard regression models including the effects of different variables on survival. CKD: chronic kidney disease. Weight change was measured from baseline to 18 months follow-up.