Abstract 437: Exploring biomarkers of metastatic breast cancer based on nanoporous silica chip for early diagnosis and therapeutic evaluation

Abstract

Abstract Breast cancer is the most frequently occurring malignancy and the second leading cause of cancer death in the United Stated and other Western countries. In these patients, not the primary tumor, but the metastasis of breast cancer caused to death. There is still a challenging to detect the metastasis in early stage and no effective target therapy at late stage metastatic breast cancer, expect the conventional chemotherapy intervention. Therefore, the identification of biomarkers for the detection of cancer metastasis in the early stage and discovery of new therapy targets may hold the key to the management of metastasis breast cancer. Although high molecular weight proteins in blood have been extensively studied, little is known about the low molecular weight (LMW) proteins and peptides due to difficulties in isolation and purification of this low abundant population. These substances may circulate at very low levels and can be difficult to detect in the presence of large abundance of proteins such as albumin. In our study, we have recently developed nanoporous chip-based technologies to separate small proteins/peptides from the large proteins in serum. We used nanoporous silica chips, with a highly periodic nanostructure and uniform pore size distribution, to isolate LMW proteins and peptides from serum of mouse model with MDA-MB-231 human breast cancer lung metastasis. The matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS) were used in profiling the LMW proteins and peptides in three distinct stages (control, early stage and late stage). All data were then carried out by principle component analysis and vertical scatter plot to identify signatures unique to different stages of cancer development. Finally, we found eight peptides significant changes during the tumor development. It is interesting that these eight candidate biomarkers can be divided into three groups. Changes on serum level of group 1 fragments can be detected from both early and late stage mice. These candidates can sever as biomarkers for detection of early stage tumor metastasis. Only one peptide was included in Group 2, which was showed the similar level in control and early stage mice, but significantly elevated in late stage mice. This fragment is indicative of late stage tumors. Level of group 3 fragments increased during tumor development, and reached peak in late stage mice. Group 3 markers could be used to guide physicians to better treat cancer patients based on their tumor progression. More detailed studies in mass sequence are needed to validate the usefulness of these biomarkers. In conclusion, the nanotechnology based silica chips provide a rapid, sensitive, reproducible and inexpensive platform that will lead to significant, personalized diagnosis and new therapies for the treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 437. doi:1538-7445.AM2012-437