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

浸润性乳腺癌中细胞周期蛋白 B2 表达升高与不良临床结果相关

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作者:Emman Shubbar, Anikó Kovács, Shahin Hajizadeh, Toshima Z Parris, Szilárd Nemes, Katrin Gunnarsdóttir, Zakaria Einbeigi, Per Karlsson, Khalil Helou

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

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.

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

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).

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