الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer is a major health problem worldwide. It is the most frequently diagnosed cancer among females both in developing and developed countries. The great impact of breast cancer regarding the morbidity and mortality necessitates the use of investigations to discover the disease in an early stage. The use of mammography has helped with screening and early diagnosis of breast cancer and till now it is the most useful tool in clinical practice especially when combined with FNAC.
Due to the disadvantages of mammography as regard to sensitivity, specificity and radiation exposure, there is a need for blood-based tests that can be used effectively for breast cancer screening and diagnosis. These tests, ideally, should have better sensitivity and specificity than mammography which excludes the use of the known tumor markers (e.g. CA 15.3, CEA) for a confident and early diagnosis of breast cancer.
With the greatest advances in proteomic technologies, we can explore the low molecular part of the plasma proteome for tumor markers. This can be done through the use of mass spectrometry to detect this portion of the proteome. The use of multiple markers increases the sensitivity and specificity and there by increases the confidence for use in early diagnosis than using a single one. Therefore, discovering a profile or panel of multiple peptides or proteins will be a great breakthrough in achieving the aim of blood-based non-invasive test for breast cancer screening and early diagnosis.
As these markers are present in the low molecular part of the proteome masked by the highly abundant proteins, there will be a need for the use an effective separation technology. The use of magnetic beads offers a great solution where these micro-chromatography particles can separate proteins based on specific physico-chemical criteria. Also, there is a need for software analysis of the data obtained from mass spectrometry for accurate determination of the most suitable profile using the relevant statistical tests. ClinProt system of Bruker Daltonics offers the best combination of magnetic beads (MBs) for sample separation, MALDI-TOF MS analyzer for data acquisition from the sample and powerful software (ClinProToolsTM) to analyze the resultant data statistically.
In our study, we used Hydrophobic Interaction chromatography HIC-8 MBs which bind proteins of the mass range 1-10 kDa, Ultraflextreme MALDI-TOF MS and ClinProToolsTM 3.0 for profile generation. We divided each group from the patients and the control subjects into two independent sets randomly: a training set (n=26) and a validation set (n=24).Using GA on the training sets, a profile of 5 peaks was discovered with a recognition capacity of 100 % and an overall cross validation of 98.33 %. External validation of this profile using the validation sets yielded sensitivity of 83.7 % of and a specificity of 83.3%.
We did not perform tandem mass spectrometry for the identification of the peptides of the profile discovered. However, we searched for their identity by comparing them to the literature published regarding the identity of mass spectrometry peaks reported in different diseases. One of the peaks was bradykinin, one was a fragment of Apolipoprotein A1and one was a truncated form of apolipoprotein C1. One of the peaks with mass 4963.9 had the best AUC when using ROC curve. However, this peak had not been identified in all the studies published which mandate its identification for better understanding of the disease.