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

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.

REGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinoma

“…In recent years, an increasing number of studies have disclosed the role of CK1ε in cancer. Existing reports showed that patients with higher CK1ε expression had a considerably better outcome than patients with lower CK1ε expression in oral squamous cell carcinoma 16 , breast cancer 17 , and colorectal cancer 18 . Additionally, Fuja et al reported that CK1ε expression was reduced in poorly differentiated tumors and increased in more benign ductal cell carcinoma in situ 19 .…”

Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells

“…On the other hand, high casein kinase 1 epsilon (CSNK1E) is correlated with better prognosis in breast cancer [ 13 ] and the loss of CSNK1E is associated with poorer prognosis in patients with low stage oral cancer and in patients with hepatocellular carcinoma [ 14 , 15 ]. Furthermore, mutations in CSNK1E decrease cell adhesion and promote cell migration in breast cancer [ 16 ].…”

Facts and myths of selective casein kinase 1ε einhibition

“…In contrast, other studies reported that a significant number of patients with a high level of CK1ε expression are the ones that have better prognosis and survival [8,22,30]. Nevertheless, this source of contradiction must be properly interpreted.…”

“…LH846 is the less studied inhibitor of the series with respect to cancer treatment. In fact, it emerged following the screening of a library of 500,000 drug-like compounds tested to identify small molecules that modulate clock function [22]. However, LH846 served to establish the role of CK1δ in yeast respiratory oscillations (which is related to circadian rhythms) [49], in the maturation of cytoplasmic 40S [50], and in genomic instability characterized by the accumulation of DNA damage and down-regulation of checkpoint kinase 1 [51].…”

“…In the current minireview, we focus on three key points we consider essential to define the scope of CK1ε as a synthetic lethal partner and its inhibitors as cancer chemotherapeutics. Firstly, the therapeutic relevance, which is open to debate with respect to its exact role in cancer, denoted by diverse studies that provided, in first glance, inconsistent results [15][16][17][18][19][20][21][22]. A second consideration is in terms of the scarce availability of selective inhibitors of CK1ε, which might explain, at least in part, the contradictions observed.…”