Abstract

Abstract Objectives: The high burden of breast cancer in women worldwide underscores the unmet potential of biomarker for early detection. New strategies and biomarkers for early detection of breast cancer are sorely needed. In this study, we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary biomarkers for the non-invasive detection of breast cancer. Methods: The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatant from patients with invasive ductal carinoma and matched controls respectively. The discovered transcriptomic and proteomic candidate biomarkers were subjected to a clinical validation using an independent sample set of 31 breast cancer (invasive ductal carcinoma, stages I and II) and 62 healthy controls. Transcriptomic biomarkers were validated by qPCR and proteomic biomarkers were validated by quantitative immuno-blot. Results: Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven mRNA biomarker candidates and two protein biomarker candidates were selected for independent validation. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. Six biomarkers have known associations with breast cancer. Conclusion: Salivary biomarkers possess discriminatory power for the detection of breast cancer, with high specificity and sensitivity. This report provides proof of concept of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers' discriminatory power paves the way for a pivotal clinical validation. Supported by NIH grant U01DE016275, U01DE017790 and R21CA126733 (DTW). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2726.

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