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

View Article: PubMed Central - PubMed

ABSTRACT

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.

Electronic supplementary material: The online version of this article (doi:10.1186/s12967-017-1178-8) contains supplementary material, which is available to authorized users.

No MeSH data available.


Serum (n = 124) versus plasma (n = 124) relative amino acid concentrations in controls. All serum amino acids have been normalized to 1, while plasma levels for each amino acid are shown as a fraction of serum. Error bars show SEM
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Fig1: Serum (n = 124) versus plasma (n = 124) relative amino acid concentrations in controls. All serum amino acids have been normalized to 1, while plasma levels for each amino acid are shown as a fraction of serum. Error bars show SEM

Mentions: We initially examined SFAA and PFAA profiles in 124 non-cancer controls (Fig. 1; Additional file 1: Table S2). Unexpectedly, there were large differences in the concentration of free amino acids in serum and plasma. Free amino acids were significantly reduced in plasma compared to serum, with a mean reduction of 40%, with all amino acids showing highly significant p values. However, the magnitude of the differences varied quite widely, ranging from a 20% reduction (glutamine) to a whopping 83% reduction (aspartate). The mean co-efficient of variation (CV) was quite similar between serum and plasma (32 vs. 31%, p = ns), suggesting that processing variability was not a factor. In ccRCC samples, the difference between serum and plasma was less, with a mean reduction of 23% (range 10–74%). The difference in behavior between control and RCC patients with regards to serum and plasma will be explored in more detail later.Fig. 1


Combination of serum histidine and plasma tryptophan as a potential biomarker to detect clear cell renal cell carcinoma
Serum (n = 124) versus plasma (n = 124) relative amino acid concentrations in controls. All serum amino acids have been normalized to 1, while plasma levels for each amino acid are shown as a fraction of serum. Error bars show SEM
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5383954&req=5

Fig1: Serum (n = 124) versus plasma (n = 124) relative amino acid concentrations in controls. All serum amino acids have been normalized to 1, while plasma levels for each amino acid are shown as a fraction of serum. Error bars show SEM
Mentions: We initially examined SFAA and PFAA profiles in 124 non-cancer controls (Fig. 1; Additional file 1: Table S2). Unexpectedly, there were large differences in the concentration of free amino acids in serum and plasma. Free amino acids were significantly reduced in plasma compared to serum, with a mean reduction of 40%, with all amino acids showing highly significant p values. However, the magnitude of the differences varied quite widely, ranging from a 20% reduction (glutamine) to a whopping 83% reduction (aspartate). The mean co-efficient of variation (CV) was quite similar between serum and plasma (32 vs. 31%, p = ns), suggesting that processing variability was not a factor. In ccRCC samples, the difference between serum and plasma was less, with a mean reduction of 23% (range 10–74%). The difference in behavior between control and RCC patients with regards to serum and plasma will be explored in more detail later.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

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.

Electronic supplementary material: The online version of this article (doi:10.1186/s12967-017-1178-8) contains supplementary material, which is available to authorized users.

No MeSH data available.