Prediction and prognostic significance of BCAR3 expression in patients with multiple myeloma

Abstract

BackgroundMultiple myeloma (MM) is the plasma cell tumor, which is characterized by clonal proliferation of tumor cells, with high risk of progression to renal impairment, bone damage and amyloidosis. Although the survival rate of patients with MM has improved in the past decade, most people inevitably relapse. The treatment and prognosis of MM are still urgent problems. Breast Cancer Antiestrogen Resistance 3 (BCAR3) is a protein-coding gene that is associated with many tumors. However, there have been few studies on the relationship of BCAR3 and MM.MethodsWe analyzed 1878 MM patients (1930 samples) from 7 independent datasets. First, we compared the BCAR3 expression level of MM patients in different stages and MM patients with different amplification of 1q21. Second, we analyzed BCAR3 expression levels in MM patients with different molecular subtypes. Finally, we explored the event-free survival rate (EFS) and overall survival rate (OS) of MM patients with high or low BCAR3 expression, including patients before and after relapse, and their therapeutic responses to bortezomib and dexamethasone.ResultsThe expression of BCAR3 showed a decreasing trend in stages I, II and III (P = 0.00068). With the increase of 1q21 amplification level, the expression of BCAR3 decreased (P = 0.022). Patients with high BCAR3 expression had higher EFS and OS (EFS: P < 0.0001, OS: P < 0.0001). The expression of BCAR3 gene before relapse was higher than that after relapse (P = 0.0045). BCAR3 is an independent factor affecting prognosis (EFS: P = 5.17E−03; OS: P = 3.33E−04).ConclusionWe found that high expression level of BCAR3 predicted better prognosis of MM patients. Low expression of BCAR3 at diagnosis can predict early relapse. BCAR3 is an independent prognostic factor for MM. BCAR3 can be used as a potential biomarker.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1728-8) contains supplementary material, which is available to authorized users.

A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics

“…Our finding that BCAR3 is subject to complex post-translational regulation may be helpful in reconciling the observation that BCAR3 over-expression in cell culture increases transformed phenotypes whereas BCAR3 RNA expression correlates with favorable outcomes in patients (Guo et al, 2014, Wallez et al, 2012, Zhang et al, 2018). In addition to the phosphorylation-dependent mechanism investigated here, a previous study showed that TGFβ stimulates proteasomal degradation of BCAR3 (Guo et al, 2014), and over-expressed BCAR3 and Cas appear to stabilize each other in breast cancer cells, dependent on their mutual binding (Wallez et al, 2014).…”

Prognostic Value and Efficacy Evaluation of Novel Drugs for Multiple Myeloma Patients with 1q21 Amplification (Amp1q21) Only: A Systematic Review of Randomized Controlled Trials

“…In an early study, the stem cell marker nestin strongly associated with the presence of 1q21 gain may play an important role in MM relapse [29]. Besides, a study in Beijing analysis a gene expression microarrays of 1878 MM patients and found that with the increase of the amplification level of 1q21, the expression level of BCAR3 which is a protein-coding gene associated with many tumors showed an overall downward trend, interestingly, the expression of BCAR3 gene was different statistically in the non-relapse group and the relapse group, and the expression in the non-relapse group was notably higher than that in the relapse group (P = 0.0023) [14]. In a word, a common view have get that the main cause of myeloma recurrence is persistent residual tumor cells, which are associated with clonal evolution and immune dysfunction.…”

“…And a study of 500 patients showed that NDMM with Amp1q21 had inferior 5-year event-free/overall survival compared with those non-Amp1q21 (38%/52% vs. 62%/78%, both P < .001), and relapsed patients who had Amp1q21 had inferior 5-year post-relapse survival compared with those lacking Amp1q21 at relapse (15% vs. 53%, P = .027) [13]. Besides, Amp1q21 as the secondary genetic events may contributes much to the relapse of myeloma, while the relapse rate may decrease if treating as early as possible [14], suggesting that an early treatment target on Amp1q21 in newly diagnosed MM (NDMM) may significantly decrease the relapse of MM patients.…”

“…What's more, Amp1q21 is always means a poor prognostic and Amp1q21 is as an independent adverse prognostic factor [7]. In 2012, the Amp1q21 was as a high risk factor according to a prognostic classification system [8]; in 2015, patients with t (4; 14) translocation and gain (1q) were classified into intermediate-risk group [6,9]; and in 2018, updated mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) combined the middle-risk and high-risk groups, and Amp1q21 was again as a poorprognostic factor for multiple myeloma. At the same time, the concept of "double-hit" and "triple-hit" was proposed (defined as that: 2 or even 3 high-risk genetic abnormalities existence the same time.)…”

RNA expression classifiers from a model of breast epithelial cell organization to predict pathological complete response in triple negative breast cancer

“…Genes from the two classifiers (Table S1) [21]. In addition, it has been shown that BCAR3 can be used as a potential biomarker, and is an independent prognostic factor for Multiple myeloma [22]. Genes involved in the extracellular matrix, such as MFAP4, were also identified in the classifiers.…”