Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome

Abstract

BackgroundBreast cancer is a potentially fatal malignancy in females despite the improvement in therapeutic techniques. The identification of novel molecular signatures is needed for earlier detection, monitoring effects of treatment, and predicting prognosis. We have previously used microarray analysis to identify differentially expressed genes in aggressive breast tumors. The purpose of the present study was to investigate the prognostic value of the candidate biomarkers CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 in breast cancer.MethodsThe expression levels and subcellular localization of the CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 proteins were measured using immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Furthermore, the mRNA levels of CCNB2, KIAA0101, and SLC27A2 were subsequently examined by qRT-PCR to validate IHC results. Patient disease-specific survival (DSS) was evaluated in correlation to protein levels using the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of aberrant protein expression of the candidate biomarkers on patient DSS and to estimate the hazard ratio at 8-year follow-up.ResultsElevated cytoplasmic CCNB2 protein levels were strongly associated with short-term disease-specific survival of breast cancer patients (≤ 8 years; P<0.001) and with histological tumor type (P= 0.04). However, no association with other clinicopathological parameters was observed. Multivariate Cox regression analysis specified that CCNB2 protein expression is an independent prognostic marker of DSS in breast cancer. The predictive ability of several classical clinicopathological parameters was improved when used in conjunction with CCNB2 protein expression (C-index = 0.795) in comparison with a model without CCNB2 expression (C-index = 0.698). The protein levels of ASPM, CDCA7, KIAA0101, and SLC27A2 did not correlate with any clinicopathological parameter and had no influence on DSS. However, a significant correlation between the expression of the CCNB2 and ASPM proteins was detected (P = 0.03).ConclusionThese findings suggest that cytoplasmic CCNB2 may function as an oncogene and could serve as a potential biomarker of unfavorable prognosis over short-term follow-up in breast cancer.

Proteomic Profiling of Diffuse Large B-Cell Lymphomas

“…Based on previous publications [15], positive immunoreactivity in lymphoma cells was defined as 1+ (weak cytoplasmic staining), 2+ (moderate staining), and 3+ (strong staining).…”

“…Cyclin B2 has been shown to be an adverse prognostic marker in breast cancer [15], but its role in lymphomas is not well studied. However, cyclin B1 has been described as a marker of poor outcome in DLBCL [22].…”

Multidrug‐resistant transporter expression does not always result in drug resistance

“…The effect of model selection, however, needs to be taken into account for interpretation of results. For instance, Longati et al noted metabolism and gene expression shifts in tumor spheroids, inducing chemoresistance 8. Also, gemcitabine‐resistant populations have been shown to harbor CSC potential after in vivo selection,9 emphasizing that the plasticity of cell phenotypes depends on experimental model.…”

Emerging optical methods for surveillance of Barrett's oesophagus

“…Genetic instability, 60 including chromosomal aberrations (aneuploidy/ tetraploidy), loss of heterozygosity, changes in DNA methylation, abnormalities in tumour suppressor loci, changes in cell cycle regulation, dysregulation of cell signalling and focal gene amplifications and deletions are believed to play important roles in the initiation and progression of disease. [61][62][63][64] Many of these changes have been identified by copy number variation on analysis with single nucleotide polymorphism arrays. 65 High-frequency gene amplification can produce overexpression of protein targets on the cell surface, cytoplasm or extracellular matrix that are accessible to imaging.…”