High casein kinase 1 epsilon levels are correlated with better prognosis in subsets of patients with breast cancer

Oncotarget. 2015 Oct 6;6(30):30343-56. doi: 10.18632/oncotarget.4850.

Abstract

Reliable biological markers that predict breast cancer (BC) outcomes after multidisciplinary therapy have not been fully elucidated. We investigated the association between casein kinase 1 epsilon (CK1ε) and the risk of recurrence in patients with BC. Using 168 available tumor samples from patients with BC treated with surgery +/- chemo(radio)therapy, we scored the CK1ε expression as high (≥ 1.5) or low (<1.5) using an immunohistochemical method. Kaplan-Meier analysis was performed to assess the risk of relapse, and Cox proportional hazards analyses were utilized to evaluate the effect of CK1ε expression on this risk. The median age at diagnosis was 60 years (range 35-96). A total of 58% of the patients underwent breast conservation surgery, while 42% underwent mastectomy. Adjuvant chemotherapy and radiation therapy were administered in 101 (60%) and 137 cases (82%), respectively. Relapse was observed in 24 patients (14%). Multivariate analysis found high expression of CK1ε to be associated with a statistically significant higher disease-free survival (DFS) in BC patients with wild-type p53 (Hazard ratio [HR] = 0.33; 95% CI, 0.12-0.91; P = 0.018) or poor histological differentiation ([HR] = 0.34; 95% CI, 0.12-0.94; P = 0.039) or in those without adjuvant chemotherapy ([HR] = 0.11; 95% CI, 0.01-0.97; P = 0.006). Our data indicate that CK1ε expression is associated with DFS in BC patients with wild-type p53 or poor histological differentiation or in those without adjuvant chemotherapy and thus may serve as a predictor of recurrence in these subsets of patients.

Keywords: breast cancer; casein kinase 1 epsilon (CK1ε); disease-free survival; outcome; relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Casein Kinase 1 epsilon / genetics
  • Casein Kinase 1 epsilon / metabolism*
  • Cell Differentiation
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Mastectomy
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Transfection
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Casein Kinase 1 epsilon