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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

Red and green zones for PCa diagnosis in 2D plot of MIC-1 and PSA.For the ease of presentation, one patient with high PSA concentration of 241.3 ng/ml was not shown. Zone A: 24 PCa and 2 nonPCa, 92.3% cases are PCa; Zone B: 9 PCa and 1 nonPCa, 90% cases are PCa; Zone C: 1 PCa and 17 nonPCa, 94.4% cases are nonPCa; Zone D: 8 PCa and 8 nonPCa. Arrows near the top and right edges of the plot indicate the concentrations of biomarkers used to define the zones.
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pone.0122249.g004: Red and green zones for PCa diagnosis in 2D plot of MIC-1 and PSA.For the ease of presentation, one patient with high PSA concentration of 241.3 ng/ml was not shown. Zone A: 24 PCa and 2 nonPCa, 92.3% cases are PCa; Zone B: 9 PCa and 1 nonPCa, 90% cases are PCa; Zone C: 1 PCa and 17 nonPCa, 94.4% cases are nonPCa; Zone D: 8 PCa and 8 nonPCa. Arrows near the top and right edges of the plot indicate the concentrations of biomarkers used to define the zones.

Mentions: Another approach to utilize the results of both the MIC-1 and PSA assays was to generate a two dimensional (2D) plot in which the MIC-1 and PSA concentrations as the X- and Y-axes and then determining distinct zones based on the varying positive predictive value (PPV) for the sample set. Compared to traditional multi-factor linear formula, a 2D plot can offer better resolution to present data and can display more information. One such plot, based on all 70 samples plotted and involving four zones, is presented in Fig 4. Zones A, C and D correspond to high, low and unbiased PPV, respectively. The PPV is 92% (24/26) in Zone A, 5.6% (1/18) in Zone C and 50% (8/16) in Zone D. Surprisingly; a small isolated “hot” Zone B can be observed where the PPV to detect PCa is very high, 90% (9/10).


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)

Red and green zones for PCa diagnosis in 2D plot of MIC-1 and PSA.For the ease of presentation, one patient with high PSA concentration of 241.3 ng/ml was not shown. Zone A: 24 PCa and 2 nonPCa, 92.3% cases are PCa; Zone B: 9 PCa and 1 nonPCa, 90% cases are PCa; Zone C: 1 PCa and 17 nonPCa, 94.4% cases are nonPCa; Zone D: 8 PCa and 8 nonPCa. Arrows near the top and right edges of the plot indicate the concentrations of biomarkers used to define the zones.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122249.g004: Red and green zones for PCa diagnosis in 2D plot of MIC-1 and PSA.For the ease of presentation, one patient with high PSA concentration of 241.3 ng/ml was not shown. Zone A: 24 PCa and 2 nonPCa, 92.3% cases are PCa; Zone B: 9 PCa and 1 nonPCa, 90% cases are PCa; Zone C: 1 PCa and 17 nonPCa, 94.4% cases are nonPCa; Zone D: 8 PCa and 8 nonPCa. Arrows near the top and right edges of the plot indicate the concentrations of biomarkers used to define the zones.
Mentions: Another approach to utilize the results of both the MIC-1 and PSA assays was to generate a two dimensional (2D) plot in which the MIC-1 and PSA concentrations as the X- and Y-axes and then determining distinct zones based on the varying positive predictive value (PPV) for the sample set. Compared to traditional multi-factor linear formula, a 2D plot can offer better resolution to present data and can display more information. One such plot, based on all 70 samples plotted and involving four zones, is presented in Fig 4. Zones A, C and D correspond to high, low and unbiased PPV, respectively. The PPV is 92% (24/26) in Zone A, 5.6% (1/18) in Zone C and 50% (8/16) in Zone D. Surprisingly; a small isolated “hot” Zone B can be observed where the PPV to detect PCa is very high, 90% (9/10).

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