Casein kinase 1 epsilon expression predicts poorer prognosis in low T-stage oral cancer patients

Abstract

Casein kinase 1 is a group of ubiquitous serine/threonine kinases that are involved in normal cellular functions and several pathological conditions, such as DNA repair, cell cycle progression, cytokinesis, differentiation, and apoptosis. Recent studies have indicated that casein kinase 1-epsilon (CK1ε) and casein kinase 1-delta (CK1δ) expression has a role in human cancers. We investigated the associations between CK1ε and CK1δ expression and the clinical parameters of oral cancer using immunohistochemical study methods on oral squamous cell carcinoma specimens. The results of our immunohistochemical analysis showed that the loss of CK1ε expression was greatly associated with a poor four-year survival rate in oral cancer patients (p = 0.002). A Kaplan-Meier analysis showed that patients who had a loss of CK1ε expression had a considerably poorer overall survival rate than patients who had positive CK1ε expressions (p = 0.022). A univariate analysis revealed that patients who had a loss of CK1ε expression had considerably poorer overall survival (OS) than patients who had positive expression (p = 0.024, hazard ratio (HR) = 1.7). In conclusion, our data indicated that the loss of cytoplasmic CK1ε expression is greatly associated with poor survival and might be an adverse survival factor.

Figure 1.

CK1ɛ and CK1δ immunoreactivity and CK1ɛ kinase activity in non-tumor oral squamous mucosa and SCC. (A) Strong cytoplasmic CK1ɛ expression in SCC (score 2+); (B) Strong cytoplasmic CK1δ expression in SCC (score 2+); (C) Weak cytoplasmic CK1ɛ expression in SCC (score 1+); (D) Weak cytoplasmic CK1δ expression in SCC (score 1+); (E) Negative CK1ɛ expression in SCC (score 0); (F) Negative CK1δ expression in SCC (score 0); (G,H) Strong cytoplasmic CK1ɛ expression in the non-tumor part than that of tumor part. Circle indicated the tumor part. Frame indicated the non-tumor part; and (I) Lower CK1ɛ kinase activity in the tumor part then that of non-tumor part. * Significant differences from control values with p < 0.05.

Figure 1.

CK1ɛ and CK1δ immunoreactivity and CK1ɛ kinase activity in non-tumor oral squamous mucosa and SCC. (A) Strong cytoplasmic CK1ɛ expression in SCC (score 2+); (B) Strong cytoplasmic CK1δ expression in SCC (score 2+); (C) Weak cytoplasmic CK1ɛ expression in SCC (score 1+); (D) Weak cytoplasmic CK1δ expression in SCC (score 1+); (E) Negative CK1ɛ expression in SCC (score 0); (F) Negative CK1δ expression in SCC (score 0); (G,H) Strong cytoplasmic CK1ɛ expression in the non-tumor part than that of tumor part. Circle indicated the tumor part. Frame indicated the non-tumor part; and (I) Lower CK1ɛ kinase activity in the tumor part then that of non-tumor part. * Significant differences from control values with p < 0.05.

Figure 2.

CK1ɛ expression in normal epithelial cell (SG cell) and four different OSCC cells lines (OC2, OECM1, SCC25 and TW206). Western blot analysis, indicating the high expression of CK1ɛ in normal epithelial cells and the low expression in OECM1 and TW206 oral cancer cells. * Significant differences from control values with p < 0.05.

Figure 3.

Kaplan-Meier survival curves for oral SCC patients who were classified with either negative or positive cytoplasmic CK1ɛ expression. Loss of CK1ɛ expression was strongly associated (log-rank, p = 0.022) with patient survival. However, no significant association was found in the stage I, stage II and stage III subgroups.

Figure 3.

Kaplan-Meier survival curves for oral SCC patients who were classified with either negative or positive cytoplasmic CK1ɛ expression. Loss of CK1ɛ expression was strongly associated (log-rank, p = 0.022) with patient survival. However, no significant association was found in the stage I, stage II and stage III subgroups.