Πέμπτη 30 Ιουνίου 2016

Low expression of centrosomal protein 78 (CEP78) is associated with poor prognosis of colorectal cancer patients

Abstract

Background

Centrosomal protein 78 (CEP78) has been characterized as a component of the centrosome required for the regulation of centrosome-related events during the cell cycle, but its role in human cancers remains unclear. This study aimed to investigate the role and the clinical value of CEP78 in colorectal cancer (CRC).

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to examine CEP78 expression in CRC tissues and adjacent noncancerous tissues. The association between CEP78 expression and clinical outcomes of CRC patients was determined. The effect of CEP78 on cell growth was examined in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, colony formation, and flow cytometry assays and in vivo using a nude mouse model.

Results

The expression level of CEP78 was significantly lower in tumor tissues than in the adjacent normal tissues (P < 0.01). Low CEP78 expression was significantly associated with poor differentiation (P = 0.003), large tumor size (P = 0.017), lymphatic metastasis (P = 0.034), distant metastasis (P = 0.029), and advanced stage (P = 0.011). Kaplan–Meier analysis indicated that patients with low CEP78 expression had shorter survival than those with high CEP78 expression (P < 0.01). Overexpression of CEP78 in CRC cells significantly reduced cell viability and colony formation in vitro and halted tumor growth in vivo. Further study showed that CEP78 reintroduction in CRC cells resulted in G2/M phase arrest rather than cell apoptosis.

Conclusions

CEP78 might function as a tumor suppressor and serve as a novel prognostic marker in CRC.



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