3044 Background: Breast cancer is the most frequently diagnosed cancer and the most leading cause of cancer-related deaths among women worldwide. Although screening mammography is available, there is an ongoing interest in improved early detection and prognosis. And also, serum tumor marker levels, such as CA 15-3 and others, may reflect disease progression and recurrence, they have not proven to be sensitive for early disease detection. Research investigating biomarkers for early detection, prognosis and the prediction of treatment responses in breast cancer is rapidly expanding. However, no validated biomarker currently exists for use in routine clinical practice, and breast cancer detection and management remains dependent on invasive procedures We aimed to develop biomarker for diagnosis of breast cancer in the real clinical practice by using proteomics technology. Methods: Based on our previous studies, we performed verification and validation of 124 candidate proteins by using proteomics approach. Among these 124 candidate proteins, the three proteins (neural cell adhesion molecule L1-like protein, apolipoprotein C-1, carbonic anhydrase-1) with highest statistical significance were selected. We created the performance algorithm of the 3-protein diagnostic model to predict of the breast cancer. We performed several experiments for establishment and validation of cut-off value. Furthermore we conducted test for acquisition of sample stability and more experiments to achieve the reproducibility and level of evidence, compared with other cancers (colon, thyroid, ovary, pancreas and lung cancer) and established effect of anesthesia. Results: Total 1226 samples (532 patients of breast cancer, 562 healthy women and 100 sample of other cancers) was analyzed. The sensitivity, specificity and accuracy from confirmation experiment was 71.58%, 85.25% and AUC 0.8323, respectively. The result of comparison with other cancers, there are no statistical significant difference and no relevance with effects of anesthesia. With these results, we recently got permission it to use for in vitro diagnostic use from Korea Food and Drug Administration. Conclusions: In this study, we developed a plasma protein biomarker that may help to diagnosis of breast cancer in the real clinical practice. By using MRM approach, the 3-protein biomarker was validated in an independent cohort with acceptable accuracy for early diagnosis of breast cancer.
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