Abstract 431: Circulating fibroblast growth factor 21 (FGF21) as diagnostic and prognostic biomarker in renal cancer

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&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 <0.01). Interestingly, we found that ccRCC patients (n = 98) have higher levels of serum FGF21 compared to HC (KW test: p<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<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.

Fibroblast growth factor 21 in patients with cardiac cachexia: a possible role of chronic inflammation

“…FGF‐21 was correlated with weight loss and anorexia, although the impact of sarcopenia was not assessed . Further, increased FGF‐21 levels are also reported in patients with renal cancer, as compared with healthy controls, and in end‐stage kidney disease, where high FGF‐21 is associated with impaired outcome . We found increased FGF‐21 levels in patients with cardiac cachexia, as well as associations between FGF‐21 and the central cardiac cachexia disorders, chronic inflammation, and muscle wasting.…”

Immunogenomic Analyses of the Prognostic Predictive Model for Patients With Renal Cancer

“…Then, a personalized, predictive nomogram with a risk score was developed, which served as a predictive indicator; the signature encompassed a total of 14 IRGs. Among these, SAA1, TNFSF14, FGF21, IFNG, BMP7, and IL11 are biomarkers for predicting RCC outcomes (67)(68)(69)(70)(71)(72). For example, as a member of the serum amyloid A family of apolipoproteins, SAA1 can increase the invasive capacity of tumor cells in RCC by inducing MMP-9 expression (73), which make it serve as a biomarker for the diagnosis and prognosis of advanced and metastatic renal cell carcinoma.…”

Immunogenomic Analyses of the Prognostic Predictive Model for Patients with Renal Cancer

“…Then, a personalized, predictive nomogram with a risk score was developed, which served as a predictive indicator; the signature encompassed a total of 14 IRGs. Among these, SAA1, TNFSF14, FGF21, IFNG, BMP7, and IL11 are biomarkers for predicting RCC outcomes [56][57][58][59][60][61]. The other IRGs, such as IL20RB, ESRRG, GDF6, and BMP7, were reported to be involved in the regulation of carcinogenesis [62][63][64][65] but not yet investigated in RCC.…”