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Macrophage inhibitory cytokine 1 biomarker serum immunoassay in combination with PSA is a more specific diagnostic tool for detection of prostate cancer.

Li J, Veltri RW, Yuan Z, Christudass CS, Mandecki W - PLoS ONE (2015)

Bottom Line: MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively).In addition, the MIC-1 level was correlated with the progression of PCa.The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies.

View Article: PubMed Central - PubMed

Affiliation: PharmaSeq, Inc., Monmouth Junction, New Jersey, United States of America.

ABSTRACT

Background: Prostate cancer (PCa) is the most common malignancy among men in the United States. Though highly sensitive, the often-used prostate-specific antigen (PSA) test has low specificity which leads to overdiagnosis and overtreatment of PCa. This paper presents results of a retrospective study that indicates that testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the PSA assay could provide much improved specificity to the assay.

Methods: The MIC-1 serum level was determined by a novel p-Chip-based immunoassay run on 70 retrospective samples. The assay was configured on p-Chips, small integrated circuits (IC) capable of storing in their electronic memories a serial number to identify the molecular probe immobilized on its surface. The distribution of MIC-1 and pre-determined PSA concentrations were displayed in a 2D plot and the predictive power of the dual MIC-1/PSA assay was analyzed.

Results: MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively). In addition, the MIC-1 level was correlated with the progression of PCa. The area under the receiver operator curve (AUC-ROC) was 0.81 providing an assay sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the logistic regression value of MIC-1 and PSA. Another approach, by defining high-frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of 78.6% and specificity of 89.3%.

Conclusions: The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies.

No MeSH data available.


Related in: MedlinePlus

ROC curves for MIC-1, PSA or MIC-1+PSA.
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pone.0122249.g003: ROC curves for MIC-1, PSA or MIC-1+PSA.

Mentions: The elevated MIC-1 level in PCa patient serum was correlated with PSA levels of the 70 serum samples (S1 Table) We therefore generated a PSA ROC curve and compared it to ROC curve for MIC-1 (Fig 3). The area under ROC (AUC-ROC) of MIC-1 was 0.776 and AUC-ROC for PSA is 0.684. However, the difference was not significant (P = 0.2431). Using multivariate logistic regression analysis for MIC-1 and PSA, we determined that a combination of the MIC-1 and PSA levels performed better in discriminating between non-PCa (normal and Bx-ve patients) and PCa. The AUC-ROC of MIC-1/PSA was 0.809 and significantly better than in the PSA only alone results (P = 0.0359) (Fig 3). By using the criterion of 0.494 for the logistic regression score of MIC-1-PSA as cutoff, we achieved the assay sensitivity of 83.3% and specificity of 60.7%. In comparison, the assay sensitivity was 54.8% and specificity was 57.1% if PSA = 4 ng/ml was used as a cutoff in the traditional PSA test, or assay sensitivity of 71.4% and specificity of 50% if PSA = 2.5 ng/ml was used as a cutoff. Thus our approach using serum MIC-1 as an additional biomarker to supplement the serum PSA results improves both sensitivity and specificity over serum PSA alone.


Macrophage inhibitory cytokine 1 biomarker serum immunoassay in combination with PSA is a more specific diagnostic tool for detection of prostate cancer.

Li J, Veltri RW, Yuan Z, Christudass CS, Mandecki W - PLoS ONE (2015)

ROC curves for MIC-1, PSA or MIC-1+PSA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390224&req=5

pone.0122249.g003: ROC curves for MIC-1, PSA or MIC-1+PSA.
Mentions: The elevated MIC-1 level in PCa patient serum was correlated with PSA levels of the 70 serum samples (S1 Table) We therefore generated a PSA ROC curve and compared it to ROC curve for MIC-1 (Fig 3). The area under ROC (AUC-ROC) of MIC-1 was 0.776 and AUC-ROC for PSA is 0.684. However, the difference was not significant (P = 0.2431). Using multivariate logistic regression analysis for MIC-1 and PSA, we determined that a combination of the MIC-1 and PSA levels performed better in discriminating between non-PCa (normal and Bx-ve patients) and PCa. The AUC-ROC of MIC-1/PSA was 0.809 and significantly better than in the PSA only alone results (P = 0.0359) (Fig 3). By using the criterion of 0.494 for the logistic regression score of MIC-1-PSA as cutoff, we achieved the assay sensitivity of 83.3% and specificity of 60.7%. In comparison, the assay sensitivity was 54.8% and specificity was 57.1% if PSA = 4 ng/ml was used as a cutoff in the traditional PSA test, or assay sensitivity of 71.4% and specificity of 50% if PSA = 2.5 ng/ml was used as a cutoff. Thus our approach using serum MIC-1 as an additional biomarker to supplement the serum PSA results improves both sensitivity and specificity over serum PSA alone.

Bottom Line: MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively).In addition, the MIC-1 level was correlated with the progression of PCa.The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies.

View Article: PubMed Central - PubMed

Affiliation: PharmaSeq, Inc., Monmouth Junction, New Jersey, United States of America.

ABSTRACT

Background: Prostate cancer (PCa) is the most common malignancy among men in the United States. Though highly sensitive, the often-used prostate-specific antigen (PSA) test has low specificity which leads to overdiagnosis and overtreatment of PCa. This paper presents results of a retrospective study that indicates that testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the PSA assay could provide much improved specificity to the assay.

Methods: The MIC-1 serum level was determined by a novel p-Chip-based immunoassay run on 70 retrospective samples. The assay was configured on p-Chips, small integrated circuits (IC) capable of storing in their electronic memories a serial number to identify the molecular probe immobilized on its surface. The distribution of MIC-1 and pre-determined PSA concentrations were displayed in a 2D plot and the predictive power of the dual MIC-1/PSA assay was analyzed.

Results: MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively). In addition, the MIC-1 level was correlated with the progression of PCa. The area under the receiver operator curve (AUC-ROC) was 0.81 providing an assay sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the logistic regression value of MIC-1 and PSA. Another approach, by defining high-frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of 78.6% and specificity of 89.3%.

Conclusions: The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies.

No MeSH data available.


Related in: MedlinePlus