title: Serum YB-1 (Y-box binding protein 1) as a biomarker of bone disease progression in patients with breast cancer and bone metastases.
abstract: YB-1 (Y-box binding protein 1) is a multifunctional cold-shock protein that has been implicated in all hallmarks of cancer. Elevated YB-1 protein level was associated with poor prognosis in several types of cancers, including breast cancer (BC), where it is a marker of decreased overall survival (OS) and distant metastasis-free survival across all subtypes. YB-1 is also secreted by different cell types and may act as an extracellular mitogen; however the pathological implications of the secreted form of YB-1 (sYB-1) are unknown. Our purpose was to retrospectively evaluate the association between YB-1 measured by ELISA in serum and disease characteristics and outcomes in patients with BC and bone metastases (BM). In our cohort, sYB-1 was detected in the serum of 22 (50%) patients, and was associated with the presence of extra-bone metastases (p=0.044). Positive sYB-1 was also associated with faster bone disease progression (HR 3.1, 95% CI 1.09-8.95, P=0.033), but no significant differences were observed concerning OS, and time to development of skeletal-related events. Moreover, patients with positive sYB-1 also had higher levels of IL-6, a known osteoclastogenic inducer. Therefore, detection of sYB-1 in patients with BC and BM may indicate a higher tumor burden, in bone and extra-bone locations, and is a biomarker of faster bone disease progression.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Ferreira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Bettencourt
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Alho
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: A L
authors.initials: AL
authors.lastname: Costa
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Sousa
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Mansinho
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Abreu
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Pulido
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Macedo
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Vendrell
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: T R
authors.initials: TR
authors.lastname: Pacheco
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Costa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Casimiro
keywords: BC, breast cancer; BM, bone metastases; BPs, bisphosphonates; Bone metastases; Breast cancer; CSD, cold shock domain; CT, computed tomography; CTCs, circulating tumor cells; CV, coefficient of variation; EMT, epithelial-to-mesenchymal transition; HCC, hepatocellular carcinoma; IL-6, interleukin 6; IQR, interquartile range; LPS, lipopolysaccharide; NTX, N-terminal telopeptide; OS, overall survival; Prognostic factor; SREs, skeletal related events; Serum biomarker; TAMs, tumor-associated macrophages; TTBP, time to bone progression; TTSRE, time to first skeletal-related event;; Y-box binding protein 1; YB-1, Y-box binding protein 1; sYB-1, secreted/serum YB-1