囊性纤维化跨膜传导调节子(CFTR)过表达与人宫颈癌恶性、进展和预后相关

Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, 20 Renmingnan Rd, Chengdu, Sichuan 610041, China

Objective: To investigate the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) to cervical cancer progression and prognosis by examining CFTR expression levels in different cervical tissues and cell lines. Methods: Paraffin-embedded cervical tissue samples (n = 192) were collected for immunohistochemistry (IHC), while fresh cervical tissue samples (n = 165) and human cervical cell lines were collected for protein and mRNA detection by quantitative real-time PCR and western blot, respectively. Correlations between CFTR expression levels to cancer clinicopathologic features and prognosis were statistically analyzed. Results: Both CFTR mRNA and protein expression gradually increased from normal to precancerous (LSIL, HSIL) and cervical cancer tissues (p < 0.05). Furthermore, CFTR expression level was well-correlated to tumor stage (p < 0.001), histological grades (p < 0.001), lymphatic metastasis (p < 0.001), vascular invasion (p < 0.05), interstitial invasive depth (p < 0.05), tumor size (p < 0.05) and HPV infection (p < 0.05). In vitro, CFTR mRNA and protein were expressed strongly both in SiHa and HeLa, but little was seen in Caski and H8 (p < 0.05). More importantly, overexpression of CFTR conferred significantly poorer survival in cervical carcinoma (Log rank p = 0.028), although it was not an independent predictor for prognosis according to multivariate analysis (p > 0.05). Conclusions: These results suggest that higher CFTR expression is closely associated with cervical cancer progression, aggressive behaviors and poorer prognosis, indicating that CFTR may function as a novel tumor marker, a prospective prognostic indicator and a potential therapeutic target for cervical cancer. © 2012 Elsevier Inc. All rights reserved.

Zhang, Y.; Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, 20 Renmingnan Rd, Chengdu, Sichuan 610041, China; email: zhangyi125@gmail.com