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.

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

“…YBX-1 has also been reported to be associated with "stem cell-like" tumor phenotype based on retrospective immunehistochemical study of paraffin-embedded breast cancer tissues [34]. A recent study reported a co-elevation of serum YBX-1 and IL-6 in breast cancer patients that was significantly correlated to bone metastasis [35].…”

“…The prognostic role of YBX-1 and IL-6 has been referred to in a number of previous studies on various types of cancers including ovarian [36], prostate [37], acute lymphoblastic leukemia [38] and multiple myeloma [39]. However, most of these studies focused on analysis of either fresh or paraffin-imbedded tissues with few exceptions which focused on minimally invasive samples like serum or plasma [35] [40]. Our results therefore support the evidence that serum YBX-1 and IL-6 levels can be used as valuable biomarkers of breast cancer with a strong potential of predicting metastasis.…”

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

“…Its role in breast cancer growth and bone metastasis was confirmed by evaluating blood samples from healthy, breast cancer, or metastatic breast cancer patients, where the higher levels of IL-6 were detected in patients with metastatic bone disease [49,50]. This higher expression of IL-6 in blood samples from patients with metastatic bone disease also correlated with high levels of Y-box-binding protein 1 expression, a multifunctional cold-shock protein [51], but not with cystatin C (Cyst C), an endogenous inhibitor of cysteine proteinase cathepsin K [52]. Increased levels of IL-6 were also highlighted in sera of mice with bone metastases [40,53], and by using a humanized 3D breast cancer bone metastasis model in which the higher levels of IL-6 were found in the presence of an osteoporotic microenvironment [43].…”

“…Nine in vitro studies also used patient peripheral venous blood and/or tumor tissue samples. Half of these studies [49,51,77,79] reported detailed demographic and clinical-pathological information such as age of primary diagnosis of breast cancer and bone metastasis, primary breast cancer histology, hormone receptor (estrogen, progesterone) and HER2 condition, breast cancer molecular subtype, sites of metastases at breast cancer presentation, if metastatic, or at time of recurrence, date and site of disease recurrence, date of bone progression, and date of skeletal-related events (SREs), while the other half reported less or no information on derived patient fluids or tissues. However, all the studies reported the patient number and the median age, and almost all (5/8) had a control group (healthy patients or breast cancer patients without bone metastases).…”

“…In vitro hFOB and MDA-MB-231 cells co-cultured on bone matrix. [51] IL-6 Blood Assess the correlation between sYB-1 and serum IL-6 in patients with breast cancer bone metastasis.…”