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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

MIC-1 level in 70 serum samples.Individual MIC-1 concentration and average in each sample group (panel A) and combined nonPCa and PCa group (panel B) is shown. Error bar represents standard deviation. Asterisk indicates P<0.05 in two-tailed unpaired t-test when the PCa group is compared to nonPCa (normal or Bx-ve group). Double asterisks indicates P<0.01 in the two-tailed unpaired t-test. Bx-ve: biopsy negative.
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pone.0122249.g002: MIC-1 level in 70 serum samples.Individual MIC-1 concentration and average in each sample group (panel A) and combined nonPCa and PCa group (panel B) is shown. Error bar represents standard deviation. Asterisk indicates P<0.05 in two-tailed unpaired t-test when the PCa group is compared to nonPCa (normal or Bx-ve group). Double asterisks indicates P<0.01 in the two-tailed unpaired t-test. Bx-ve: biopsy negative.

Mentions: In samples from the control group (normal) and Bx-ve patients the mean concentrations of MIC-1 were 0.93 ng/ml and 0.88 ng/ml, respectively (Table 1 and Fig 2), with no significant differences between the two groups (P = 0.726). The mean MIC-1 concentration in PCa patients with PSA <2.5 ng/ml was 1.24 ng/ml and significantly higher than in the normal (P = 0.039) and Bx-ve groups (P = 0.027). The mean MIC-1 concentrations in the other PCa patients groups (PSA 2.5–10 ng/ml and PSA > 10 ng/ml) were 1.35 ng/ml and 1.72 ng/ml, respectively, and also significantly higher than normal (P = 0.031 and P < 0.001, respectively) and the Bx-ve group (P = 0.022 and P < 0.001 respectively). When all the PCa cases and non-PCa cases were combined into two groups, the average MIC-1 concentration was significantly higher in the PCa patients than the group without PCa (0.90 ng/ml v.s. 1.44 ng/ml, P < 0.001). The MIC-1 serum concentration in each of the 70 samples can be found in S1 Table.


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)

MIC-1 level in 70 serum samples.Individual MIC-1 concentration and average in each sample group (panel A) and combined nonPCa and PCa group (panel B) is shown. Error bar represents standard deviation. Asterisk indicates P<0.05 in two-tailed unpaired t-test when the PCa group is compared to nonPCa (normal or Bx-ve group). Double asterisks indicates P<0.01 in the two-tailed unpaired t-test. Bx-ve: biopsy negative.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4390224&req=5

pone.0122249.g002: MIC-1 level in 70 serum samples.Individual MIC-1 concentration and average in each sample group (panel A) and combined nonPCa and PCa group (panel B) is shown. Error bar represents standard deviation. Asterisk indicates P<0.05 in two-tailed unpaired t-test when the PCa group is compared to nonPCa (normal or Bx-ve group). Double asterisks indicates P<0.01 in the two-tailed unpaired t-test. Bx-ve: biopsy negative.
Mentions: In samples from the control group (normal) and Bx-ve patients the mean concentrations of MIC-1 were 0.93 ng/ml and 0.88 ng/ml, respectively (Table 1 and Fig 2), with no significant differences between the two groups (P = 0.726). The mean MIC-1 concentration in PCa patients with PSA <2.5 ng/ml was 1.24 ng/ml and significantly higher than in the normal (P = 0.039) and Bx-ve groups (P = 0.027). The mean MIC-1 concentrations in the other PCa patients groups (PSA 2.5–10 ng/ml and PSA > 10 ng/ml) were 1.35 ng/ml and 1.72 ng/ml, respectively, and also significantly higher than normal (P = 0.031 and P < 0.001, respectively) and the Bx-ve group (P = 0.022 and P < 0.001 respectively). When all the PCa cases and non-PCa cases were combined into two groups, the average MIC-1 concentration was significantly higher in the PCa patients than the group without PCa (0.90 ng/ml v.s. 1.44 ng/ml, P < 0.001). The MIC-1 serum concentration in each of the 70 samples can be found in S1 Table.

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