Abstract

Abstract Epidemiological studies have suggested a close link between obesity and breast cancer. There is an immediate need to investigate the potential pathways linking obesity and breast cancer to have an early diagnosis in patients and optimize the chance of cure. FGF21 is a regulator of local and systemic metabolic homeostasis and its expression is induced in response to diverse physiological or pathological stressors. High serum levels of FGF21 were found in obese individuals, subjects with metabolic syndrome, type 2 diabetes mellitus and coronary heart disease. Up to date, the clinical implication of FGF21 in cancer was not elucidated. Our aim was to study the role of serum FGF21 as a diagnostic biomarker of breast cancer. The serum levels of FGF21 in 45 breast cancer women patients (median age 59, range 32-88 years) and 51 age-matched healthy controls were evaluated using a quantitative ELISA test (R&D Systems, Inc.). Patients’ samples [Stage (S) SI: 17; SII: 17; SIII: 6; ND: 5] were obtained before surgery, without any previous treatment. We included patients with carcinoma in situ (n = 2), invasive ductal (n = 31) and lobular (n = 8), special carcinoma (n = 2), ND: 2. We observed that breast cancer patients showed significantly elevated values of serum FGF21 (median 224.55 pg/ml, range 24.15-776.19) respect to the levels observed in healthy controls (76.86, 0.00-425.60) (KW and MW, p<0.0001). On the basis of the optimal cut-off point of 76.86 pg/ml serum FGF21, 37/45 breast cancer patients showed higher levels of FGF21 versus 26/51 healthy controls. The assay in our population exhibited a sensitivity of 95% and a specificity of 50%. Interestingly, we observed that serum FGF21 significantly increased since the early-stages of the disease. On the other hand, we didn't find any significant associations between the serum FGF21 levels and the clinic pathological variables relevant in breast cancer nor overall survival. We did not observe a significant association between the circulating lipid profile and the serum FGF21 levels (Spearman, NS). Our data showed a tendency that suggests that FGF21 is associated with the Disease Free Survival. Moreover, a second population of clear cell renal cell cancer (ccRCC) was included, taking into account that ccRCC is considered a cell metabolic disease associated with obesity. We observed that ccRCC patients (n = 98) showed significantly elevated values of serum FGF21 (median: 211.18 pg/ml, range 28.55-222.88) respect to the levels observed in healthy controls (MW, p<0.01). No difference was observed between serum FGF21 levels in ccCRR and breast cancer populations. We conclude that serum FGF21 has a potential use as a high sensitive diagnostic biomarker for early detection of breast cancer and ccRCC. This fact is highly relevant due to the lack of diagnostic biomarkers for these diseases and could significantly improve the overall survival rate of these cancer patients. Citation Format: Maria Elena Knott, Stella Maris Ranuncolo, Myriam Nuñez, Eduardo Armanasco, Lydia Ines Puricelli, Mariana Silvia De Lorenzo. Levels of Fibroblast Growth Factor 21 (FGF21) in serum as diagnostic biomarker in patients with breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1577. doi:10.1158/1538-7445.AM2015-1577

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