Clinicopathological Significance Of CK1α Expression In Esophageal Squamous Cell Carcinoma

Objective:Casein kinase 1α(CK1α) is a member of serine/threonine protein kinases, which expressed in all kinds of eukaryotes, and the sequence structure is highly conserved. In mammals, CK1α is involved in a variety of cellular physiological processes and partial signaling pathways. It has been shown that CK1α acts as a tumor suppressor and it is closely related to the occurrence and development of tumor. However, little is known about its role in esophageal squamous cell carcinoma(ESCC). The aim of present study was to explore the role and the prognostic significance of CK1α expression in ESCC, and to provide another theoretical basis for the development of new molecular targeted therapy of esophageal cancer.Methods:The expression of CK1α was detected by tissue microarray combined with immunohistochemistry(IHC) SP technique in 100 cases of ESCC and their corresponding adjacent normal esophageal mucosas(n=80), and analyzed the relationship between CK1α expression and clinicopathological parameters, survival rate and prognosis of ESCC patients. We preliminary investigated the expression of CK1α in 30 ESCC and their corresponding adjacent normal esophageal mucosas by RT-PCR in m RNA level.Results:1. Tissue microarray and immunohistochemistry results: The positive percentage of CK1α protein in ESCC was 56%(56/100), which was significantly lower than that in normal esophageal mucosa was 90%(72/80),(χ2=25.010, P=0.000).2. The expression of CK1α was significantly related with differentiation degree(P<0.05), but not with the sex, age, tumor size, depth of invasion, lymphatic invasion and AJCC clinical stage(P>0.05).3. On the basis of univariate and multivariate Cox regression analysis, we found that tumor size and depth of invasion were independent risk factors for worse prognosis in ESCC patients.4. Furthermore, survival analysis date revealed that the positive expression of CK1αhad significantly better survival than the negative expression of CK1α in ESCC patients after curative surgery.5. RT-PCR test results: Compared with the adjacent normal esophageal mucosas,the CK1α m RNA level was significantly lower in ESCC,the difference was statistically significant(P<0.05).Conclusion:1. These results suggest that the expression of CK1α is lower in ESCC than in nonneoplastic esophageal tissues,which is closely related with the differentiation degree of tumor.2. The positive expression of CK1α had better survival than the negative expression of CK1α in ESCC patients after curative surgery.3. Tumor size and depth of invasion are risk factors affecting survial in ESCC patients, which could be used as an independent indicator of prognosis of esophageal squamous cell carcinoma.4. Above these suggest that CK1α may be a potential tumor suppressor factor,which play an important role in the carcinogenesis and development of ESCC and might provide clinically useful prognostic information in cases of ESCC.