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Identifying New Biomarkers for Breast Cancer using Antibody Microarray Staining
Detection, Diagnosis and Prognosis
Background: A new type of protein microarray—“dissociable antibody microarray” has been developed. Instead of capturing ligands on the array support, dissociable microarrays deliver multiple antibodies to their antigens in a position-addressable manner. The dissociable antibody microarray technique has combined the power of immunohistochemical staining and the parallel analysis of antibody microarrays. The technology can provide a novel approach in global analysis of protein expressions and subcellular localizations, and be used for identifying new biomarkers for cancer diagnosis. Objective: This proposal intends to use the antibody microarray technique to obtain the molecular images of 400 - 1000 proteins in different breast cancer cell lines and tissue samples, and to identify new biomarkers for cancer diagnosis. Specific aims: 1. Determine the protein expression profiles and molecular images of 400 to 1000 proteins in 50 breast carcinoma cell lines and benign cell lines; 2. Determine the protein expression profiles and molecular images of those 400 to 1000 proteins in 100 tissue samples, for breast carcinoma and benign tissues; 3. Develop a prototype image database from the above molecular images, and identify new biomarkers for breast cancer diagnosis. Study designs/Potential Outcomes: The dissociable antibody microarrays with 100-400 antibodies have been developed in Hypromatrix Inc and have been applied in the PI’s lab to study the molecular mechanism of the tumor suppressing function of SHP-1. For this proposal, 50 different breast carcinoma and benign cell lines will be purchased from ATCC. The antibody microarray will be used to obtain the expression profiles and subcellular localizations of 400-1000 proteins in those 100 cell lines. In the second year, we shall collaborate with Dr. Zhong Jiang, a pathologist at UMASS Medical School, and obtain 100 tissue samples of breast carcinoma and benign patients. Antibody microarray staining will be used to obtain the protein expression profiles and subcellular localizations of the 400-1000 proteins in the tissue samples. The proposal is directly related to diagnosis, treatment and prognosis of breast cancer and will contribute to early diagnosis of this disease.
Breast cancer is the most common form of cancers in women. Screening programs have increased the number of women in which invasive or noninvasive breast cancer has been diagnosed. Earlier detection and better treatment have also led to improved prognosis. As the high popularity of breast cancer patients, any new molecular biomarkers for breast cancer, especially the molecular biomarkers for clinical stages assignment will be very useful for breast cancer diagnosis, treatment and prognosis. This proposal intends to identify new biomarkers from the database that accumulates the molecular images of hundreds or even thousands of proteins in samples from both breast cancer cell lines and carcinoma tissue samples, using the antibody microarray staining technique co-developed in the PI’s lab and Hypromatrix Inc. We shall first demonstrate the application of the technique on different breast cancer cell lines. After that, we shall obtain the expression profiles and molecular images of 400 to 1000 proteins of the tissue samples from breast carcinoma patients and benign breast patients and identify novel biomarkers for cancer diagnosis from the database. The specific aims in this proposal are: Determine the expression profiles and molecular images of 400 to 1000 proteins in 50-100 breast carcinoma and benign cell lines, and in 100 tissue samples from breast carcinoma and benign tissues; Develop a prototype image database from the above molecular images, and identify new biomarkers for breast cancer diagnosis. Dissociable microarray is a novel powerful tool for studying the molecular images of proteins on a scale that is impossible using conventional analysis. This technique makes it possible to examine the expression and subcellular localization of thousands of proteins simultaneously, so that we can compare their differences between cancer and normal cells at the same time. This technology can lead improvements in developing rational approaches to therapy as well as improvements in cancer diagnosis and prognosis. It will help doctors to diagnose the breast cancer patients on an earlier stage. The consumer-related outcome can be achieved in 3-5 years.