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