Abstract A32: A role for elevated leptin, independent of obesity, in the progression of melanoma
Authors: Junna Oba, Chandrani Chattopadhyay, Jeffrey E. Gershenwald, Marcella M. Johnson, Julie A. Ellerhorst, Elizabeth A. Grimm
Journal: Cancer Research (2015)

Abstract Background: With the growing epidemic of obesity in developed nations, considerable interest has been generated in the metabolic hormone leptin. Upon caloric intake, leptin is secreted by adipocytes and detected as a satiety signal in the hypothalamus. Obese individuals tend to have higher levels, likely due to hormone resistance. Less well-known is leptin's role as a pro-inflammatory adipokine. Leptin bears structural homology to type I cytokines. A wide range of pro-inflammatory functions for leptin has been published, generating interest in leptin's role in obesity-related cancers. Leptin receptors have been described in cancer of the breast, prostate, colon, and endometrium, and leptin has been implicated as a growth and invasion factor for these malignancies. We have reported that both leptin and its receptor are expressed by melanoma tumors and cell lines. Melanoma cells respond to leptin by activating the MAPK (mitogen-activated protein kinase) pathway and by proliferating. These data implicate leptin in melanoma growth and progression, and raise the possibility of an autocrine loop. Objective: In the current study we further test the hypothesis that leptin is a growth factor for melanoma by correlating leptin levels with positive and negative sentinel lymph nodes (SN). Patients and Methods: Eligible patients were high-risk primary cutaneous melanoma, within eight weeks of resection, and a SN biopsy scheduled. Clinical information included gender, age, height, weight, Clark level, Breslow thickness, mitotic index, and ulceration. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. To account for the role of obesity, an adjusted leptin was calculated for each patient by dividing the fasting (raw) leptin value with the BMI. A fasting blood sample for leptin was drawn preoperatively on the morning of surgery. Leptin levels were measured in duplicate using Quantikine Human Leptin ELISA Kit (R&amp;D Systems, Minneapolis, MN). Leptin values were transformed to the logarithmic scale for analysis. A logistic regression model was used to predict SN status using leptin and other clinical factors. A backward elimination procedure was used to identify a final model with only significant predictors remaining. Breslow thickness was kept in the final model to demonstrate the effect of leptin after adjusting for these data. Tests were two-sided and p-values of 0.05 or less were considered statistically significant. Analyses were performed using both adjusted and raw leptin. Results: Seventy-two patients were evaluated in this study. Fifteen were SN positive and fifty-seven were disease-free. Patients with positive SN had significantly higher raw and adjusted leptin levels than those with negative SN. Obesity was not accountable for the differences in leptin levels between these two sets of patients, since they had nearly identical BMIs. In the univariate regression model, significant clinical features included raw and adjusted leptin. In the multivariate logistic models predicting positive SN, raw and adjusted leptin levels remained significant. Conclusion: Elevated leptin levels are associated with metastasis of melanoma to local nodes. In this study, obesity did not account for the leptin elevations, and a tumor-related source or process must be considered. Supported by the MD Anderson Cancer Center SPORE in Melanoma P50 CA093459, the MD Anderson's Cancer Center Support Grant P30- CA016672, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and funds from the Polo on the Prairie event. Citation Format: Junna Oba, Chandrani Chattopadhyay, Jeffrey E. Gershenwald, Marcella M. Johnson, Julie A. Ellerhorst, Elizabeth A. Grimm. A role for elevated leptin, independent of obesity, in the progression of melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A32.