Limits...
Detection of Alpha-Methylacyl-CoA Racemase (AMACR), a Biomarker of Prostate Cancer, in Patient Blood Samples Using a Nanoparticle Electrochemical Biosensor.

Lin PY, Cheng KL, McGuffin-Cawley JD, Shieu FS, Samia AC, Gupta S, Cooney M, Thompson CL, Liu CC - Biosensors (Basel) (2012)

Bottom Line: However, no accurate clinically useful assay has been developed.This study reports the development of a single use, disposable biosensor for AMACR detection.Human blood samples were used to verify its validity, reproducibility and reliability.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science & Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. ppl3@case.edu.

ABSTRACT
Although still commonly used in clinical practice to screen and diagnose prostate cancer, there are numerous weaknesses of prostate-specific antigen (PSA) testing, including lack of specificity and the inability to distinguish between aggressive and indolent cancers. A promising prostate cancer biomarker, alpha-methylacyl-CoA racemase (AMACR), has been previously demonstrated to distinguish cancer from healthy and benign prostate cells with high sensitivity and specificity. However, no accurate clinically useful assay has been developed. This study reports the development of a single use, disposable biosensor for AMACR detection. Human blood samples were used to verify its validity, reproducibility and reliability. Plasma samples from 9 healthy males, 10 patients with high grade prostatic intraepithelial neoplasia (HGPIN), and 5 prostate cancer patients were measured for AMACR levels. The average AMACR levels in the prostate cancer patients was 10 fold higher (mean(SD) = 0.077 (0.10)) than either the controls (mean(SD) = 0.005 (0.001)) or HGPIN patients (mean(SD) = 0.004 (0.0005)). At a cutoff of between 0.08 and 0.9, we are able to achieve 100% accuracy in separating prostate cancer patients from controls. Our results provide strong evidence demonstrating that this biosensor can perform as a reliable assay for prostate cancer detection and diagnosis.

No MeSH data available.


Related in: MedlinePlus

Pathway from Pristanic Acid to Pristanoyl-CoA then to producing H2O2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4263563&req=5

biosensors-02-00377-f001: Pathway from Pristanic Acid to Pristanoyl-CoA then to producing H2O2.

Mentions: Pristanic acid possess four methyl groups [28,29]. Based on the reaction mechanism in Figure 1, pristanic acid can be employed as reaction substrate, which consists of two epimers designated as (2R) and (2S). Both (2R) and (2S) epimers can react with proper quantities of coenzyme A (CoA), ATP and Mg2+ in the presence of very long chain fatty acid-coenzyme A (VLCFA-CoA) synthetase forming (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, respectively. However, the (2R)-pristanoyl-CoA cannot carry out the b-oxidation process. On the other hand, (2S)-pristanoyl-CoA in the presence of the enzyme ACOX3 (peroxisomalacyl-coenzyme A oxidase 3) can carry out the b-oxidation process producing H2O2. H2O2 can be oxidized electrochemically generating a current which can then be used to quantify (2S)-pristanoyl-CoA. AMACR converts (2R)-pristanoyl-CoA to (2S)-pristanoyl-CoA, resulting in a higher H2O2 level, and the oxidation current of H2O2 can then be used to quantify the amount of AMACR present.


Detection of Alpha-Methylacyl-CoA Racemase (AMACR), a Biomarker of Prostate Cancer, in Patient Blood Samples Using a Nanoparticle Electrochemical Biosensor.

Lin PY, Cheng KL, McGuffin-Cawley JD, Shieu FS, Samia AC, Gupta S, Cooney M, Thompson CL, Liu CC - Biosensors (Basel) (2012)

Pathway from Pristanic Acid to Pristanoyl-CoA then to producing H2O2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263563&req=5

biosensors-02-00377-f001: Pathway from Pristanic Acid to Pristanoyl-CoA then to producing H2O2.
Mentions: Pristanic acid possess four methyl groups [28,29]. Based on the reaction mechanism in Figure 1, pristanic acid can be employed as reaction substrate, which consists of two epimers designated as (2R) and (2S). Both (2R) and (2S) epimers can react with proper quantities of coenzyme A (CoA), ATP and Mg2+ in the presence of very long chain fatty acid-coenzyme A (VLCFA-CoA) synthetase forming (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, respectively. However, the (2R)-pristanoyl-CoA cannot carry out the b-oxidation process. On the other hand, (2S)-pristanoyl-CoA in the presence of the enzyme ACOX3 (peroxisomalacyl-coenzyme A oxidase 3) can carry out the b-oxidation process producing H2O2. H2O2 can be oxidized electrochemically generating a current which can then be used to quantify (2S)-pristanoyl-CoA. AMACR converts (2R)-pristanoyl-CoA to (2S)-pristanoyl-CoA, resulting in a higher H2O2 level, and the oxidation current of H2O2 can then be used to quantify the amount of AMACR present.

Bottom Line: However, no accurate clinically useful assay has been developed.This study reports the development of a single use, disposable biosensor for AMACR detection.Human blood samples were used to verify its validity, reproducibility and reliability.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science & Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. ppl3@case.edu.

ABSTRACT
Although still commonly used in clinical practice to screen and diagnose prostate cancer, there are numerous weaknesses of prostate-specific antigen (PSA) testing, including lack of specificity and the inability to distinguish between aggressive and indolent cancers. A promising prostate cancer biomarker, alpha-methylacyl-CoA racemase (AMACR), has been previously demonstrated to distinguish cancer from healthy and benign prostate cells with high sensitivity and specificity. However, no accurate clinically useful assay has been developed. This study reports the development of a single use, disposable biosensor for AMACR detection. Human blood samples were used to verify its validity, reproducibility and reliability. Plasma samples from 9 healthy males, 10 patients with high grade prostatic intraepithelial neoplasia (HGPIN), and 5 prostate cancer patients were measured for AMACR levels. The average AMACR levels in the prostate cancer patients was 10 fold higher (mean(SD) = 0.077 (0.10)) than either the controls (mean(SD) = 0.005 (0.001)) or HGPIN patients (mean(SD) = 0.004 (0.0005)). At a cutoff of between 0.08 and 0.9, we are able to achieve 100% accuracy in separating prostate cancer patients from controls. Our results provide strong evidence demonstrating that this biosensor can perform as a reliable assay for prostate cancer detection and diagnosis.

No MeSH data available.


Related in: MedlinePlus