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

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.