Overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) is associated with human cervical cancer malignancy, progression and prognosis

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• 作者：Xue Peng^a ; ^b ; ^c ; ¹ ; Zhao Wu^a ; ^b ; ^c ; ¹ ; Lei Yu^a ; ^b ; ^c ; Jinke Li^a ; ^b ; ^c ; Wenming Xu^d ; Hsiao Chang Chan^d ; ^e ; Yi Zhang^a ; ^c ; ^{zhangyi125@gmail.com} ; Lina Hu^a ; ^{cqhulina2011@yahoo.cn}
• 关键词：Cystic fibrosis transmembrane conductance regulator (CFTR) ; Cervical cancer ; Tumor progression ; Survival
• 刊名：Gynecologic Oncology
• 出版年：2012
• 期刊代码：295_00908258
• 类别：med
• 出版时间：May, 2012
• 卷：125
• 期：2
• 页码：470-476
• 文件大小：760 K

摘要

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.