Evaluation of MIC-1 (DD-X065) as a serum diagnostic biomarker for ovarian cancer Free

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Using microarray and quantitative RT-PCR analyses on various cancer and normal tissues, we found DD-X065 mRNA to be up-regulated in breast, colon, lung, ovarian, and prostate cancer tissues. DD-X065 is known in the literature as macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor-beta (TGF-β) family. We have developed a sensitive ELISA for MIC-1 and have previously shown that serum MIC-1 levels are also significantly elevated in serum samples from breast, colon, lung, ovarian and prostate cancer patients.¹ In this study, we evaluated elevation of MIC-1 levels in serum samples from ovarian cancer patients.

MIC-1 is synthesized as a precursor form which is processed by a furin-like protease to yield the mature MIC-1 protein, a disulfide-linked homodimer. We have previously shown that mature MIC-1 was readily detectable in human serum, whereas the precursor form was not. The ELISA assay for the mature form was used to measure MIC-1 levels in serum samples from 80 normal healthy individuals and 80 ovarian cancer patients. The sensitivity and specificity of the assay for detection of ovarian cancer were analyzed using receiver operating characteristic (ROC) analysis. Compared to normal healthy individuals, the median serum concentration of MIC-1 was increased by approximately 1.6 fold in ovarian cancer, irrespective of stage. ROC analysis of ovarian cancer patients versus normal healthy individuals resulted in an AUC of 0.735 in all stages, AUC = 0.790 in late stage (stages III+IV) cancers (N=54), and AUC = 0.708 in early stage (stages I+II) cancers (N=26).

Our study suggests that MIC-1 is a promising serum marker for ovarian cancer that may improve the detection rate of early stage cancers. Further studies are underway to validate the clinical potential of this marker.

¹Fan RA, Krall KL, Kim NW et al., (2006) Proceedings of 97^th AACR Annual Meeting, Washington, D.C.