Genomics, Proteomics and Cancer: Specific Ribosomal,Mitochondrial, and Tumor Reactive Proteins Can Be Used as Biomarkers for Early Detection of Breast Cancer in Serum

摘要

We have used genomics and proteomics based technologies to study tissue and serum protein profiles in patients with breast cancer (BC) in comparison to control healthy subjects. One critical objective of this study was to identify and characterize new tissue and serum biomarkers of BC using differential screening of a recombinant cDNA human BC expression library. A second major objective of this study was to evaluate the clinical utility of Metallolpanstimulin (MPS-1/S27 ribosomal) protein as a biomarker for the early detection and monitoring of BC by immunoassay measurements of serum MPS-1 protein levels and to identify MPS-1 protein in sera of BC patients. A third objective was to present data on cloned BC genes denoted protein subgroup-30 (PS-30), consisting of mitochondria, nuclear, and ribosomal proteins which are increased after growth factor stimulation of BC cells in tissue culture. To study^ in detail MPS-1 protein expression in BC, the MPS-1 concentrations were determined in the blood of 117 females free of any disease, and in 203 female patients diagnosed with primary BC. The results indicate that increased serum MPS-1 levels can be used for the early detection of BC. Normal subjects have low concentrations of MPS-1 protein in sera. Moreover, changes in MPS-1 protein serum levels can be used for the study of BC progression or regression after various types of therapy. In both the low and high value range, MPS-1 is 10-fold more effective than CA-15-3 in modifying the probability of the target condition -breast cancer. The use of HPLC, Western blot, Immuno-Mass Spectrometry, and protein sequencing confirmed the presence of authentic MPS-1 in sera of patients with BC. Negligible levels of MPS-1 protein were detected in sera from normal subjects. We conclude that (1) the increase in serum MPS-1 can be used for the early detection of BC; and (2) MPS-1 proved to be reliable in the follow-up of patients with advanced BC as demonstrated by the close correlation between MPS-1 protein levels and BC progression or regression after various types of therapy. Furthermore, all proteins denoted group -30 (Mr <30,000), consisting of ribosomal, nuclear and mitochondria proteins, were found to be significantly increased in BC tissues in comparison to control tissues, suggesting that these proteins may be useful markers for detection of BC. Finally, several serum reactive proteins such as haptoglobin and C3 complement components provided valuable information on oncogenic activity in BC patients.