Identification and validation of plasma protein biomarker panels for breast cancer diagnosis by using multiple reaction monitoring-based mass spectrometry.
10621 Background: Multiple reaction monitoring-based mass spectrometry (MRM-MS) has the ability to perform a wide range of proteome analysis in a single experiment using a small volume of specimen. We aimed to develop a plasma protein signature for breast cancer diagnosis using the MRM-MS technology. Methods: Previously, we have identified lists of breast cancer-related proteins from various models of proteomic discovery including cancer plasma vs healthy plasma, cancer cell line secretome vs non-tumorigenic cell line secretome, cancer tissue vs normal tissue, and literature search. Based on these protein panels, total of 29 proteins were selected for further experiments. We verified and validated the protein signature in two independent cohorts of breast cancer patients and healthy women. Results: In the verification cohort of 80 breast cancer patients and 80 healthy women, MRM-MS showed significant differences in plasma concentration for 11 proteins. Among them, the difference was not significant for 4 proteins when the cases were limited to stage I and II patients. Based on p values and consistent expression level along the AJCC stages, we have created a plasma protein signature comprised of 3 plasma proteins. The 3 plasma protein signature effectively discriminated cancer and healthy cases with the AUC of 0.831 (sensitivity 78.7%, specificity 78.7%). The performance of the 3 plasma protein signature was validated in the cohort of 100 cancer patients and 100 healthy women. The accuracy of the 3 protein signature was still meaningful with the AUC of 0.746 and 0.797 for all stages and stage I or II patients, respectively. Conclusions: The 3 plasma protein signature for breast cancer diagnosis, developed by the MRM-MS technology, showed promising results in the present study.