CYLD expression in benign, malignant and metastatic lesions of colorectal epithelium and its prognostic role in colorectal carcinoma

Dysregulation of the cylindromatosis (CYLD) gene has been involved in various cancer entities, including colorectal carcinoma (CRC). However, the expression profile and clinical significance of CYLD in patients with a series of colorectal lesions are yet to be clear. In this study, we analyzed the difference of CYLD gene expression among 19 normal colorectal mucosae, 60 colorectal adenoma tissues, 170 primary CRC tissues, 20 lymph nodes metastases and 20 liver metastases and investigated the association of CYLD expression in CRC patients with clinicopathological variables and prognostic significance using immunohistochemistry. We observed that CYLD expression was gradually downregulated from normal tissues, through benign colorectal adenoma, as well as invasive carcinoma, to metastatic lesions of CRC. Low CYLD expression in CRC was significantly correlated with poor differentiation, T3/4 invasion depth, positive lymph node metastasis, vessel embolus, perineural invasion and advanced TNM stage (P < 0.01). Kaplan-Meier survival analysis showed that CRC patients with low CYLD expression survived significantly shorter than patients with high CYLD expression (P = 0.001). Cox multivariate analysis revealed that low CYLD expression was an independent poor prognosis factor in CRC patients (HR = 1.723, 95% CI = 1.029-2.884, P = 0.039). In conclusion, CYLD expression is evidently downregulated across both the colorectal adenoma-carcinoma sequence and the metastatic process, suggesting a role in tumorigenesis, tumor progression and metastasis. Moreover, CYLD may serve as a new potential prognostic target in patients with CRC.