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

BMC Cancer

Emman Shubbar⁴  Anikó Kovács²  Shahin Hajizadeh²  Toshima Z Parris¹  Szilárd Nemes¹  Katrin Gunnarsdóttir³  Zakaria Einbeigi¹  Per Karlsson¹  Khalil Helou¹ 

[1] Sahlgrenska Cancer Center, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SE-41345, Sweden

[2] Pathology section, Department of Pathology, Sahlgrenska University Hospital, Gothenburg, SE-41345, Sweden

[3] Regional Cancer Centre (West), Western Sweden Health Care Region, Sahlgrenska University Hospital, Gothenburg, SE-41345, Sweden

[4] Sahlgrenska Cancer Center, Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg SE-41345, Sweden

关键词: Prognostic marker;    Invasive breast carcinoma;    CCNB2;   

Others  :  1079989
DOI  :  10.1186/1471-2407-13-1

 received in 2012-07-24, accepted in 2012-12-17,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Shubbar et al.; licensee BioMed Central Ltd.

【 图 表 】

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