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

ABSTRACT: BACKGROUND: Breast 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. METHODS: The 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. RESULTS: Elevated 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). CONCLUSION: These 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.

SUBMITTER: Shubbar E

PROVIDER: S-EPMC3545739 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Shubbar Emman E Kovács Anikó A Hajizadeh Shahin S Parris Toshima Z TZ Nemes Szilárd S Gunnarsdóttir Katrin K Einbeigi Zakaria Z Karlsson Per P Helou Khalil K

BMC cancer 20130102

<h4>Background</h4>Breast 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, ...[more]

PMID: 23282137

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Project description:BackgroundTrkC, a member of neurotrophin receptor family, functions not only as an oncogene, but also act as a tumor suppressor via a manner of dependence receptor in human malignant tumors. Little is known on the action of TrkC for the clinical prognosis and the progression of breast cancer according to the availability of its ligand NT-3. We sought to investigate the prognostic relevance of NT-3-TrkC axis in breast cancer and estimate its role during the process of breast cancer progression.Methods236 cases of invasive ductal carcinoma (IDC), 60 pure ductal carcinoma in situ (DCIS) and 30 normal breast tissue (NBT) between 2004 and 2005 were included in the study. Spearman's rank correlation test was used to analyze the association of NT-3-TrkC expression and breast cancer progression. The Kaplan-Meier method and Cox proportional hazards model were performed to identify the relevant prognostic factors.Results50.4% IDC tumors displayed absent or low TrkC expression, while 49.6% was high TrkC expression. TrkC expression was negatively associated with lymph node metastasis (P = 0.029) and tumor proliferation (P = 0.015). Patients with lower TrkC expressing tumors had a higher risk of recurrence (odds ratio, 0.401; 95% confidence interval, 0.207-0.778; P = 0.007). The layered analysis indicated that patients with high TrkC expression tumors had a favor disease-free survival whether NT-3 and TrkC were co-expressed or solitarily expressed in the tumor (P = 0.000). NT-3 was demonstrated to be not a predictor of IDC patients' prognosis. But NT-3 expression was inversely correlated with the progression of breast cancer (r = -0.341, P = 0.000), since more IDC tumors showed high NT-3 expression than DCIS tumors (51.7% vs. 25.9%), while no NBT showed high NT-3 expression, as well.ConclusionThe study indicates TrkC expression reduces tumor relapse independent of NT-3 availability in the IDC. Elevated NT-3 expression contributes to the progression of breast cancer.

Project description:BackgroundIncreasing evidence has indicated that the nuclear receptor subfamily 3 group C member 2 (NR3C2) may be associated with tumorigenesis and patient prognosis for certain types of tumors. However, the clinical significance of NR3C2 is unclear in invasive breast carcinoma (BRCA).MethodsWe used bioinformatics to broadly investigate and obtain a deeper understanding of the prognostic significance between NR3C2 and BRCA. RNA-sequencing data and clinical information of patients with BRCA from the Cancer Genome Atlas database were collected for subsequent analysis. The diagnostic efficacy of NR3C2 was evaluated by calculating the receiver operating characteristic curve. The prognostic value of NR3C2 was evaluated by Kaplan-Meier analysis and Cox regression analysis for patients with BRCA. Moreover, the OSbrca database was used to validate NR3C2 as a prognostic biomarker for BRCA. Gene set enrichment analysis (GSEA) and tumor immune infiltration analysis were conducted to explore the molecular mechanism of NR3C2 in BRCA.ResultsThe expression level of NR3C2 in BRCA tissues decreased compared to that in normal breast tissues (P < 0.001). NR3C2 presented good diagnostic efficacy (AUC = 0.908). Moreover, the expression of NR3C2 was verified using the Oncomine database. High expression of NR3C2 was statistically associated with prolonged overall survival (HR = 0.65, 95% CI: 0.47-0.91, and P = 0.012), progression-free interval (HR = 0.68, 95% CI: 0.49-0.95, and P = 0.024), and disease-specific survival (HR = 0.57, 95% CI: 0.36-0.89, and P = 0.015) for patients with BRCA. Besides, the prognostic value of NR3C2 was verified by the OSbrca database. GSEA results suggested that enriched pathways included neuroactive ligand-receptor interaction, focal adhesion, and ECM-receptor interaction. NR3C2 expression was moderately correlated with mast cells and some T cell subsets in BRCA.ConclusionNR3C2 is a potential prognostic biomarker that could help clinicians develop more appropriate treatment plans for individual patients with BRCA.

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

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

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