Combination of serum histidine and plasma tryptophan as a potential biomarker to detect clear cell renal cell carcinoma

Background: In previous work, we showed that serum-free amino acid (SFAA) profiles were different between kidney cancer patients and age and sex matched controls. The goals of the current study are to: (1) confirm our initial observation on an independent sample set; (2) examine if there were similar differences in plasma-free amino acids (PFAA); and (3) determine if removal of tumors changed SFAA and PFAA profiles. Methods: SFAA and PFAA profiles were measured in 484 samples taken from 124 healthy controls and 56 clear cell renal cell carcinoma (ccRCC) patients both before and after resection of renal tumors. Results: SFAA and PFAA profiles taken from identical blood samples were remarkably different, with the mean individual amino acid concentrations being 40% less in plasma compared to serum. Both SFAA and PFAA profiles differed significantly between ccRCC patients and controls, but the individual amino acids that differed the most, and the direction of the changes, were quite different between the two blood components. Removal of the tumor had almost no effect on either the SFAA or PFAA profiles. A logistic regression model using serum histidine and plasma tryptophan correctly classified 85.5% of control and 84.7% of case samples. Conclusions: Our findings show that that tumor mass is not directly linked to alterations in blood amino acid levels, and that a combination of serum histidine and plasma tryptophan may be useful as a biomarker to detect ccRCC.