Detection of Lysyl Oxidase-Like 2 (LOXL2), a Biomarker of Metastasis from Breast Cancers Using Human Blood Samples.

Abstract

Metastasis accounts for 90% of the mortality associated with breast cancer. Upregulated expression of members of the lysyl oxidase (LOX) family of secreted copper amine oxidases catalyzes the crosslinking of collagens and elastin in the extracellular matrix. LOXs are linked to the development and metastatic progression of breast cancers. Accordingly, aberrant expression of LOX-like 2 (LOXL2) is observed in poorly differentiated, high-grade tumors and is predictive of diseases recurrence, and for decreased overall patient survival. Therefore, LOXL2 expression may serve as a biomarker for breast cancer. Mechanistically, hydrogen peroxide is produced as a byproduct of LOXL2 when using an appropriate substrate, lysine. We exploited this chemistry to generate a revolutionary gold-based electrochemical biosensor capable of accurately detecting nanomolar quantities of LOXL2 in mouse blood, and in human blood samples. Two different sources of the blood samples obtained from breast cancer patients were used in this study indicating the applicability of detecting LOXL2 in breast cancers patients. Limited numbers of urine specimens from breast cancer patients were also tested. Collectively, all of these tests show the promise and potential of this biosensor for detecting LOXL2 as a surrogate biomarker of breast cancer. This work is described in WO 052962 A1 (2014).