TY - JOUR
T1 - The Urinary Proteome Differs with the Presence and Type of Breast Cancer
AU - Zainurin, Nur Aimi Aliah
AU - Morphew, Russell M.
AU - Ganti, Alekhya
AU - Ivanova, Dimitra
AU - Gate, Tim
AU - Tench, Helen
AU - Phillips, Helen
AU - Pennick, Mandana
AU - Mur, Luis A. J.
PY - 2025/11/3
Y1 - 2025/11/3
N2 - 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), = 46, (2) benign breast disease (BBD), = 36, (3) symptom control (SC), = 30, and (4) healthy control (HC), = 18. The BC class included preinvasive: ductal carcinoma in situ (DCIS) ( = 3), invasive ductal carcinoma (IDC) ( = 23), and IDC accompanied by DCIS ( = 8) classes. Protein profiling was performed using ThermoScientific ProteomeDiscoverer and analyzed using MetaboAnalyst v6.0, DAVID, and STRING v12.0. Analyses identified 346 significantly ( < 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 ( < 0.05). Thus, BC has distinct urinary-protein profiles based on clinical diagnosis, which could be used in real-time noninvasive BC monitoring.
AB - 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), = 46, (2) benign breast disease (BBD), = 36, (3) symptom control (SC), = 30, and (4) healthy control (HC), = 18. The BC class included preinvasive: ductal carcinoma in situ (DCIS) ( = 3), invasive ductal carcinoma (IDC) ( = 23), and IDC accompanied by DCIS ( = 8) classes. Protein profiling was performed using ThermoScientific ProteomeDiscoverer and analyzed using MetaboAnalyst v6.0, DAVID, and STRING v12.0. Analyses identified 346 significantly ( < 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 ( < 0.05). Thus, BC has distinct urinary-protein profiles based on clinical diagnosis, which could be used in real-time noninvasive BC monitoring.
KW - breast cancer
KW - benign breast disease
KW - symptom controls
KW - proteomics
KW - biomarkers
KW - urine
U2 - 10.1021/acs.jproteome.5c00229
DO - 10.1021/acs.jproteome.5c00229
M3 - Article
C2 - 41181894
SN - 1535-3893
JO - Journal of Proteome Research
JF - Journal of Proteome Research
ER -
