Which Cyclin E Prevails as Prognostic Marker for Breast Cancer? Results from a Retrospective Study Involving 635 Lymph Node–Negative Breast Cancer Patients

Abstract

Purpose: To evaluate the prognostic value of cyclin E with a quantitative method for lymph node^negative primary breast cancer patients. Patients and Methods: mRNA transcripts of full-length and splice variants of cyclin E1 (CCNE1) and cyclin E2 (CCNE2) were measured by real-time PCR in frozen tumor samples from 635 lymph node^negative breast cancer patients who had not received neoadjuvant or adjuvant systemic therapy. Results: None of the PCR assays designed for the specific splice variants of the cyclins gave additional prognosis-related information compared with the common assays able to detect all variants. In Cox multivariate analysis, corrected for the traditional prognostic factors, high levels of cyclin E were independently associated with a short distant metastasis-free survival [hazard ratio (HR), 3.40; P < 0.001 for CCNE1 and HR, 1.76; P < 0.001 for CCNE2, respectively]. After dichotomizing the tumors at the median level of 70% tumor cells, the multivariate analysis showed particularly strong results for CCNE1 in the group of 433 patients with stroma-enriched primary tumors (HR, 5.12; P < 0.001). In these tumors, the worst prognosis was found for patients with estrogen receptor^negative tumors expressing high CCNE1 (HR, 9.89; P < 0.001) and for patients with small (T 1 ) tumors expressing high CCNE1 (HR, 8.47; P < 0.001).Conclusion: Our study shows that both CCNE1 and CCNE2 qualify as independent prognostic markers for lymph node^negative breast cancer patients, and that CCNE1 may provide additional information for specific subgroups of patients.

Analysis of breast cancer related gene expression using natural splines and the Cox proportional hazard model to identify prognostic associations

“…For VEGF and CCNE2 it is known that tumors progress more rapid and have a poor prognosis when these genes are over expressed [19,24,26,31,32]. This is in agreement with our results showing that higher expression levels of these genes are associated with poorer disease outcome in a linear fashion.…”

Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes

“…Similar effects have been reported with another potent anticancer phytochemical indole-3-carbinol, which attenuates CDK2 activity and matrix metalloproteinase 2 expression [40,41]. Elevated expression of cyclin E has also been shown to correlate with poorer prognosis, increased genomic instability, as well as higher grade of tumors [42]. In addition, the percentage of E2F1-positive cells increased positively with increasing stages of breast cancer [43], which likely controls the expression levels of CDK2 and cyclin E in late stage cancers.…”

Stemness gene expression profile analysis in human umbilical cord mesenchymal stem cells

“…Overexpression Table 3 Genes for which expression levels in UC-MSCs were ,10-fold lower than that in KMB17, BEL-7404 and SPC-A-1 cells of this gene, which results in chromosome instability, has been observed in many tumors, and thus may contribute to tumorigenesis. 45,46 MYST2 regulates gene expression by intimately connecting to post-translational modification of histones bound to DNA. It has central and specific roles in regulating cellular processes ranging from apoptosis, cell cycle and adult stem cell homeostasis, to patterning of the early embryo.…”