The Urinary Proteome Differs with the Presence and Type of Breast Cancer

Despite advancements in screening and treatment, the incidence of breast cancer (BC) and associated mortality are projected to increase. Therefore, developing a companion diagnostic for BC remains important. Herein, we explore the urinary proteome for biomarkers of BC: 130 urine samples from (1) newly diagnosed breast cancer (BC), <i>n</i> = 46, (2) benign breast disease (BBD), <i>n</i> = 36, (3) symptom control (SC), <i>n</i> = 30, and (4) healthy control (HC), <i>n</i> = 18. The BC class included preinvasive: ductal carcinoma in situ (DCIS) (<i>n</i> = 3), invasive ductal carcinoma (IDC) (<i>n</i> = 23), and IDC accompanied by DCIS (<i>n</i> = 8) classes. Protein profiling was performed using ThermoScientific ProteomeDiscoverer and analyzed using MetaboAnalyst v6.0, DAVID, and STRING v12.0. Analyses identified 346 significantly (<i>p</i> < 0.05) differentially expressed proteins (DEP) across BC, BBD, SC, and HC. Multivariate Receiver Operating Characteristic curves (five proteins) suggested Area Under the Curve values of 0.985, 0.989, and 0.999 distinguishing BC from BBD, SC, and HC, respectively. DEP elevated in BC included beta-glucuronidase isoform 1, fibrinogen gamma chain, alpha-actinin-1, peptidase inhibitor 16, cysteine-rich C-terminal protein 1 isoform X1, guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, vascular cell adhesion protein 1, ATP-dependent translocase ABCB1, and tumor protein p63-regulated gene 1 isoform X1. BC types were differentiated based on calpain-2 and cystatin-C expression (<i>p</i> < 0.05). Thus, BC has distinct urinary-protein profiles based on clinical diagnosis, which could be used in real-time noninvasive BC monitoring.