Abstract
Renal cell carcinoma (RCC) is the second most lethal urinary cancer. RCC is frequently asymptomatic and it is already metastatic at diagnosis. There is an urgent necessity for RCC specific biomarkers selection for diagnostic and prognostic purposes. In present study, we applied liquid chromatography—mass spectrometry (LC-MS) based metabolomics to analyze urine samples of 100 RCC, 34 benign kidney tumors and 129 healthy controls. Differential metabolites were analyzed to investigate if urine metabolites could differentiate RCC from non-RCC. A panel consisting of 9 metabolites showed the best predictive ability for RCC from the health controls with an area under the curve (AUC) values of 0.905 for the training dataset and 0.885 for the validation dataset. Separation was observed between the RCC and benign samples with an AUC of 0.816. RCC clinical stages (T1 and T2 vs. T3 and T4) could be separated using a panel of urine metabolites with an AUC of 0.813. One metabolite, N-formylkynurenine, was discovered to have potential value for RCC diagnosis from non-RCC subjects with an AUC of 0.808. Pathway enrichment analysis indicated that tryptophan metabolism was an important pathway in RCC. Our data concluded that urine metabolomics could be used for RCC diagnosis and would provide candidates for further targeted metabolomics analysis of RCC.
Highlights
Renal cell carcinoma (RCC) is the second most lethal urinary cancer and accounts for 5% of all adult malignancies [1]
Potential biomarkers for RCC were further explored based on differential metabolites and were validated using 10-fold cross validation or external validation
The relative content of N-formylkynurenine showed a 1.67-fold increase compared to the healthy control group and showed a 2.07fold increase compared to the benign control group. These results suggest that accumulation of N-formylkynurenine in RCC patients’ urine may be used as a potential biomarker for RCC diagnosis
Summary
Renal cell carcinoma (RCC) is the second most lethal urinary cancer and accounts for 5% of all adult malignancies [1]. Dynamic contrast-enhanced computed tomography (CT) provides an accurate diagnosis of RCC in most cases. Some small carcinomas are difficult to confirm. Differentiating benign kidney tumors from RCC still remains a clinical challenge, even when images are re-examined by experienced radiologists. Final confirmation of RCC requires pathological examination of puncture or surgical resection. 20–30% of small renal masses that are surgically removed are found to be benign [2]. The development of new, accurate, non-invasive diagnostic methods will have an important impact in RCC clinical management in its earliest stage and could reduce unnecessary treatment for benign tumors and increase the chance of nephron-sparing treatment
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