The prognostic value of the Tau protein serum level in metastatic breast cancer patients and its correlation with brain metastases

Abstract

BackgroundMetastatic breast cancer (MBC) prognosis is variable, depending on several clinical and biological factors. A better prediction of a patient’s outcome could allow for a more accurate choice of treatments. The role of serum biomarkers in predicting outcome remains unclear in this setting. Tau, a microtubule-associated protein, is a neuronal marker that is also expressed in normal breast epithelial cells and cancer cells. Its tissue expression is associated with prognosis in MBC. However, the prognostic value of Tau serum levels in these patients is unknown. We aimed at evaluating the prognostic value of Tau (and other classical biomarkers) in MBC patients, and to assess its association with the presence of brain metastases (BM).Methods244 MBC patients treated at our institution (2007–2015) were retrospectively selected. The usual MBC clinical and pathological variables were collected, altogether with CA15–3, CEA and HER2 extra-cellular domain (ECD) serum levels. Tau serum levels were measured with a novel immunoassay (digital ELISA) using Single Molecule Array (Simoa) technology. Overall survival (OS) was estimated with the Kaplan-Meier method. To investigate prognostic factors, a multivariate analysis was performed. Cut-offs were set using the Youden index method associated with receiver-operating characteristics (ROC) curves to evaluate the accuracy of biomarkers to identify patients with BM.ResultsWith a median follow-up of 40.8 months, median OS was 15.5 months (95%CI 12.4–20.2). Elevated serum levels of Tau were independently associated with a poor outcome in the whole population as well as in patients with (n = 86) and without BM (n = 158). Median serum Tau levels tended to be higher in patients with BM (p = 0.23). In univariate analysis, patients with BM had an increased risk of serum Tau > 3.17 pg/mL (OR = 2.2, p = 0.049). In multivariate analysis, high values of Tau (OR = 3.98, p = 0.034) accurately identified patients with BM in our cohort.ConclusionsTau is a new biomarker of interest in MBC. Its serum level could represent an independent prognostic factor in these patients (both with and without BM). It also seems to be associated with the presence of BM. A validation of these results in an independent set of MBC patients is necessary to confirm these findings.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5287-z) contains supplementary material, which is available to authorized users.

Exploring Relationships Among Peripheral Amyloid Beta, Tau, Cytokines, Cognitive Function, and Psychosomatic Symptoms in Breast Cancer Survivors

“…Frisardi et al, 2010;Tucsek et al, 2014). It also supports findings that more aggressive and heterogenous BC tumors express APPs and, consequently, require more complex treatment regimens (Ames et al, 2014;Darlix et al, 2019;Pandey et al, 2016). We found no correlations between concentrations of Ab-42, Ab-40, and tau and those of the 13 cytokines.…”

“…Over the past decade, researchers have studied peripheral Ab and tau mostly within the context of neurodegeneration, brain injury, and cognitive impairment. Recently, however, oncology research has begun to consider these factors in relation to breast tumor characteristics and brain metastases (Darlix et al, 2019).…”

“…In preclinical models, researchers have found increased expression of APP in BC cell lines, especially in those that possess higher metastatic potential, reporting significant correlations between the level of APP and tumor development in BC tissues (Lim et al, 2014). Studies have linked tau to metastatic BC as well (Darlix et al, 2019).…”

Bioinformatics Analysis and Identification of the Expression and Mechanism of Immune-related Gene MAPT in Hepatocellular Carcinoma

“…( Figure 8A , although its exact molecular mechanism and function in cancer have not yet been elucidated. Besides, many studies showed that the aberrant expression of MAPT in many cancers, such as neuroblastoma, breast, and prostate cancer 6,7,25 . Nonetheless, the survey about MAPT in HCC was still lacking.…”

“…Previous research demonstrated that higher serum levels of MAPT were independently related to poor prognosis in patients with metastatic breast cancer 6 .…”