Prognostic and clinicopathological value of ZIC1 in patients with cervical squamous cell carcinoma.

The aim of the present study was to analyze the differences in zinc finger of the cerebellum 1 (ZIC1) expression between cervical cancer tissue, precancer tissue and normal cervical tissue to determine its clinicopathological and prognostic value in cervical squamous cell carcinoma (CSCC). Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of ZIC1 in 569 fresh-frozen biopsy tissues, and immunohistochemistry was performed to detect ZIC1 protein expression in 80 CSCC tissues and 320 cervical intraepithelial neoplasia (CIN) grade III samples. The association of ZIC1 expression with the clinicopathological characteristics of CSCC was then analyzed using Cox regression analysis, and Kaplan-Meier curves were used to analyze the prognostic value. The level of ZIC1 mRNA expression in CSCC was significantly lower compared with normal cervical tissues and CIN I-III tissues (P<0.001). There was a negative correlation between ZIC1 immunoreactivity score (IRS) in CSCC tissue and adjacent noncancerous tissue (R=-0.279; P=0.012); the mean IRS of ZIC1 in CSCC tissue was 5.36±3.48, which was significantly lower compared with the corresponding adjacent noncancerous tissues (11.31±5.68; P<0.001) and CIN III samples (10.42±1.54; P<0.001). In addition, expression of ZIC1 was negatively associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.027) and lymph node metastasis (P<0.001). In Cox regression analysis, ZIC1 expression [hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.40-0.92; P=0.018), FIGO staging (HR, 3.55; 95% CI, 2.35-5.37; P<0.001) and lymph node metastasis (HR, 2.50; 95% CI, 1.62-3.86; P<0.001) were three independent prognostic factors of overall survival. Furthermore, ZIC1 expression was also associated with disease-free survival (P=0.003). These results suggest that ZIC1 expression in CSCC may be lower than in normal cervical tissues or CIN tissues, and high expression of ZIC1 may be negatively associated with FIGO stage and lymph node metastasis. Therefore, ZIC1 may be a promising biomarker for the prognosis of CSCC.