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

Artikel i vetenskaplig tidskrift
Författare Emman Shubbar
Anikó Kovács
Shahin Hajizadeh
Toshima Z Parris
Szilard Nemes
Katrin Gunnarsdóttir
Zakaria Einbeigi
Per Karlsson
Khalil Helou
Publicerad i BMC cancer
Volym 13
Nummer/häfte 1
Sidor 1
ISSN 1471-2407
Publiceringsår 2013
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Sahlgrenska Cancer Center
Sidor 1
Språk en
Länkar dx.doi.org/10.1186/1471-2407-13-1
https://gup.ub.gu.se/file/186516
Ämnesord CCNB2, Invasive breast carcinoma, And prognostic marker
Ämneskategorier Medicinska grundvetenskaper, Cancer och onkologi

Sammanfattning

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.

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