| Breast cancer is one of the main malignant forms of cancer for women. Its incidence increases year by year in China and it has become the most familiar caner of women in the big cities such as Beijing, Tianjin and Shanghai etc. In the past ten years, the death rate of breast cancer in China improved about 40%. Even the diagnosis and treatment of breast cancer are much improved these years, but they are not satisfying yet. Currently, the main diagnostic measures of breast cancer are self-examination, clinical/physical examination and imaging examination such as mammography, ultrasonic imaging, etc. Nevertheless, these classical methods do little for patients whose tumors are small or non-palpable. On the other hand, mammography is more suitable for western women than for oriental women because the galactophores of the latter are more compact and there is less adipose tissue in their breasts than in those of the former. Presently, the evaluation of curative effects, the estimation of prognosis and follow-up mainly depend on the before-mentioned, traditional methods too. Nevertheless, they are also not satisfying. In some sense, these problems are due to the lack of good tumor biomarkers for breast cancer in fact. Current serum tumor biomarkers such as CA15.3, CA27.29, and CEA etc. have many disadvantages. Their positive rates are all rare low and cannot get high sensitivities and specificities at the same time. Their diagnostic value at early stage for breast cancer are very poor and only have a little significance to the monitoring of recurrence and metastasis. Therefore, it is urgent to find sensitive, specific, and convenient new biomarkers.Protein but not nuclear acid is the material executant and embodiment of life. So, the studies on proteomics are preferred to approach to the pathogenesis of breast cancer and screen sensitive and specific biomarkers. A novel technology, surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) carved out such a new path to proteomics research on breast cancer. It can directly obtainhigh-throughput protein profilings from clinical samples with high sensitivity and this is the main advantage of this technology.With the rapid development of life science, large quantities of data were obtained from genomics and proteomics fields. It is almost impossible to analysis so much data only by traditional mathematic and statistic methods. So bioinformatics is applied to collect, deposit and analysis the data and screen the useful information.Three parts compose this study. Firstly, screen serum tumor biomarkers and found diagnostic models of breast cancer by SELDI-TOF-MS and bioinformatics tools. Secondly, establish the protocols for tissue protein profilings by SELDI-TOF-MS and screen the discrepant proteins between the tissues of breast cancer and normal galactophore. Lastly, bioinformatics tools were utilized to analyze the data from cDNA microarrays of breast cancer. The purposes of this study are to screen novel tumor biomarkers of breast cancer that are fit for diagnosis in early stage and monitoring of recurrence and metastasis, to provide materials and elements for the further studies such as the separation, purification and decoding of biomarkers and the preparation of mono-clone antibodies and tumor vaccines, to provide new ideas of pathogenesis of breast cancer and to lay the bioinformatics ground for the combined detection of SELDI-TOF-MS and cDNA microarray.Part 1: The Application of Serum Protein Fingerprints in the Diagnosis of Breast CancerThe coefficients of variation of three kinds of proteinchips were compared and CM 10 chip was chose for the detection of serum protein fingerprints. The protein fingerprints of 139 serum samples (63 cases of breast cancer, 36 cases of benign breast disease and 40 cases of healthy women) were detected by SELDI-TOF-MS and CM 10 chip. T-test and Mann-Whitney rank test were utilized to analysis the data after the pre-treatment such as calibration, filtration of noise and clustering. The discrepant...
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