Evaluation of human secretoglobins and MIC-1 as serum diagnostic biomarkers for breast cancer.

Abstract

Abstract Abstract #2005 Using microarray and quantitative RT-PCR analysis, we found mRNA corresponding to several members of the human secretoglobin family and MIC-1 to be highly expressed in various cancer tissues, as compared to the corresponding normal tissues. Our target ECM2, known in the literature as Lipophilin B (LipB), was found to be upregulated in endometrial, uterine, breast and prostate cancer tissues. Our target ECM3, also known as Mammaglobin B (MamB) or Lipophilin C, was found to be upregulated in endometrial and uterine cancer tissues. DD-X065, also known in the literature as macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor-beta (TGF-b) family, was found to be upregulated in breast, colon, lung, ovarian, and prostate cancer tissues.
 There is considerable evidence suggesting that members of the secretoglobin family exist predominantly as heterodimers and higher order complexes. Mammaglobin A (MamA) protein has been found to be present in breast tissue in a complex with LipB protein. We generated a series of mouse monoclonal antibodies directed against different complexes composed of members of the family, including MamA, LipB, and MamB. Employing these specific antibodies, we have developed sensitive immunoassays to measure serum levels of several of the complexes.
 In the current study, we evaluated serum from breast cancer patients for levels of two secretoglobin family complexes: MamA/LipB and MamB/LipB, as well as for MIC-1, utilizing our previously established ELISA assay2.
 The study comprised serum samples from 150 normal healthy individuals and 250 breast cancer patients. The sensitivity and specificity of the assays for detection of breast cancer were quantified by receiver operating characteristic (ROC) analysis. Compared to normal healthy individuals, the median serum concentrations of MamA/LipB was increased by approximately 2.8 fold in breast cancer, irrespective of stage. ROC analysis of breast cancer patients versus normal healthy individuals resulted in an AUC of 0.67 in all stages. For MamB/LipB, the median serum concentration in cancer serum was increased over normals by approximately 1.8 fold and the corresponding AUC was 0.62. The median serum concentration for MIC-1 in cancer serum was increased over normals by approximately 1.1 fold and the corresponding AUC was 0.61. The sensitivity of the MIC-1 assay was greater than that of any of the secretoglobin family complex assays at 90%, 95% and 98%.
 Our study suggests that MIC-1 and members of the secretoglobin family may be promising serum markers for breast cancer. Their utility may be improved when used in combination with other novel diagnostic biomarkers. Further studies are underway to validate the clinical potential of this family of markers.
 2Bistrup, A, et al., (2007) Proceedings of 98th AACR Annual Meeting, Los Angeles, CA. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2005.