Abstract 1827: Detection of recurrent renal cell carcinoma biomarkers by metabolite ratios
Authors: Sanchez-Espirdion Beatriz , Tannir Nizar M. , Matin Surena F. , Karam Jose A. , Huang Maosheng , Wood Christopher G. , Wu Xifeng , Gu Jian 
Published: August 2015

Abstract
Background: Renal cell carcinoma (RCC) can be cured surgically if detected at early stages. Nevertheless, approximately 30% of patients experience local recurrence or distant metastasis. The identification of biomarkers for the early detection of recurrent RCC has great potential to reduce its mortality. Plasma metabolites are emerging as promising minimally invasive biomarkers for the early detection and prognostication in cancers including RCC.
Methods: We performed global metabolomic profiling on 180 clear cell RCC (ccRCC) plasma samples that were split into discovery and validation sets comprising each 45 ccRCC cases with recurrence and 45 without recurrence matched on age, gender and blood collection time. The ratios of metabolite concentrations as proxies for enzymatic reaction rates were calculated. Wilcoxon-rank sum test was used to compare the metabolite ratio levels between cases with and without recurrence. Multivariable logistic regression analysis was used to assess the association between plasma metabolite ratios and ccRCC recurrence.
Results: A total of 791 metabolites were detectable in the plasma samples, with 522 metabolites remaining after quality control procedures. When metabolite ratios were analyzed, 373 metabolite ratios showed consistent differential levels between ccRCC recurrent cases and non-recurrent cases in the discovery and validation sets (p &lt;0.05; q &lt;0.05) with 16 ratios showing significance at p &lt;10−6. Further exploratory analyses of these 16 top relevant metabolite ratios showed a key role for metabolic pathways involving lysolipids and sphingolipids, aminoacids metabolism, pyrimidine metabolism and cofactors and vitamins metabolism as associated with RCC recurrence. Out of the 16 top relevant metabolite ratios, 7 ratios were significantly associated with ccRCC recurrence by logistic regression analyses. When using the median value as cut-off point, higher levels of the aminoacids ratio were associated with a 5.18-fold (95% confidence interval (CI), 1.93-13.91; p = 0.001) and 3.68-fold (95% CI, 1.32-10.27; p = 0.013) for the discovery and validation set respectively. Similarly, higher levels of the lysolipids ratio were associated with a 4.09-fold (95% CI, 1.52-10.97; p = 0.005) and 3.77-fold (95%CI, 1.39-10.25; p = 0.002) for discovery and validation set respectively.
Conclusion: This is the first study to evaluate plasma metabolite ratios and RCC recurrence by a global metabolomic approach. Metabolite ratios including specific aminoacids and lysolipids are potential biomarkers for RCC recurrence.
Citation Format: Beatriz Sanchez-Espirdion, Nizar M. Tannir, Surena F. Matin, Jose A. Karam, Maosheng Huang, Christopher G. Wood, Xifeng Wu, Jian Gu. Detection of recurrent renal cell carcinoma biomarkers by metabolite ratios. [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 1827. doi:10.1158/1538-7445.AM2015-1827