Abstract 431: Circulating fibroblast growth factor 21 (FGF21) as diagnostic and prognostic biomarker in renal cancer
Authors: Maria Elena Knott, Jose Nicolas Minatta, Lucia Roulet, Guillermo Gueglio, Leonardo Pasik, Stella Maris Ranuncolo, Myriam Nuñez, Lydia Ines Puricelli, Mariana Silvia De Lorenzo
Journal: Cancer Research (2016)

Abstract Clear-cell renal cell carcinoma (ccRCC), the most frequent renal parenchyma malignant neoplasm, is considered a cell metabolic disease. The finding of new biomarkers is needed for better sub-classification of renal cell tumors as well as reliable predictors of outcome and therapy response. Fibroblast Growth Factor 21 (FGF21) is a hepatokine that regulates glucose, energy and lipid metabolism during stress-induced pathologies. Despite the beneficial effects of FGF21 in diabetes and obesity; up to date, the clinical implication of FGF21 as a cancer biomarker was not investigated. Our main goal was to evaluate the role of circulating FGF21 as a diagnostic and prognostic biomarker for ccRCC. Initially, we measured the levels of circulating FGF21 in human healthy controls (HC, n = 51) using a quantitative ELISA test (R&amp;D Systems, Inc.). No associations were observed between FGF21 serum concentration and gender or age. FGF21 levels significantly correlated only with triglycerides levels (Spearman's test: p &amp;lt;0.01). Interestingly, we found that ccRCC patients (n = 98) have higher levels of serum FGF21 compared to HC (KW test: p&amp;lt;0.0001). FGF21 serum levels were not associated with BMI or other metabolic parameters. Using 130.64 pg/ml of serum FGF21 as a cut-off value, the sensitivity was 80.61% and the specificity was 64.61%. Serum FGF21 was increased since the earliest stages of the disease without differences among the various ccRCC stages. To analyze the associations between FGF21 and clinico-pathological parameters; FGF21 values were dichotomized into “low” or “high” using 219.57 pg/ml (50th percentile) as cut-off point. No significant association was observed with age, sex, obesity, triglycerides and known risk factors (Chi square test, NS). The prognostic value of FGF21 was analyzed in terms of disease-free survival (DFS) and overall survival (OS). No significant association was found between serum FGF21 levels and 5- years OS. Kaplan-Meier plots of DFS showed that high levels of serum FGF21 were associated with worse prognosis with a borderline significance. However, multivariate analysis showed that FGF21 expression is a significant independent prognostic factor when adding the variables Fuhrman grade and stage (Cox Regression test). We also collected a second serum sample in 30 patients after successful surgery and we observed that the levels of serum FGF21 decreased in 41.4% of ccRCC patients. In addition, we showed that serum FGF21 levels were significantly increased in 14 patients with chromophobe renal cancer respect to HC (MW test: p&amp;lt;0.0001), although similar to RCC patients. Our results indicated that serum FGF21 is useful as a diagnostic ccRCC biomarker in combination with other clinical or molecular parameters. Moreover, in our cohort of ccRCC patients, high levels of FGF21 showed to be an independent prognostic biomarker, associated with worse disease-free survival. Citation Format: Maria Elena Knott, Jose Nicolas Minatta, Lucia Roulet, Guillermo Gueglio, Leonardo Pasik, Stella Maris Ranuncolo, Myriam Nuñez, Lydia Ines Puricelli, Mariana Silvia De Lorenzo. Circulating fibroblast growth factor 21 (FGF21) as diagnostic and prognostic biomarker in renal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 431.