Tumour cell expression of C4.4A, a structural homologue of the urokinase receptor, correlates with poor prognosis in non-small cell lung cancer

Abstract

C4.4A expression has been implicated in human cancer progression. This protein is a structural homologue of the urokinase receptor, uPAR, which constitutes a well-established prognostic marker in various human cancers. Nonetheless, little is known about the prognostic significance of C4.4A expression. In the present study, we therefore explored the possible association between C4.4A expression and prognosis in patients with non-small cell lung cancer (NSCLC). Tissue sections from 108 NSCLC patients were subjected to immunohistochemical staining using a polyclonal antibody that specifically recognises human C4.4A. Staining frequency and intensity was scored semiquantitatively and grouped into cancers with high and low expression of C4.4A. Kaplan-Meier survival curves were generated to evaluate the significance of C4.4A expression in prognosis of NSCLC patients. High C4.4A expression was observed in 42% of the NSCLC specimens analysed, and this correlates with overall survival (p = 0.012). A remarkably strong correlation was noted between high expression of C4.4A in pulmonary adenocarcinoma and survival (p < 0.0001). Multivariate Cox regression analysis shows that high C4.4A expression is an independent predictor of poor disease outcome in NSCLC (risk ratio, 1.42; 95% confidence interval, 1.09-1.86; p = 0.009). Although histological type is not a predictor of outcome in NSCLC, high C4.4A expression in adenocarcinoma is nevertheless a very strong predictor of poor disease outcome (risk ratio, 1.62; 95% confidence interval, 1.24-2.09; p = 0.001). High tumour cell C4.4A expression is associated with shorter survival for NSCLC patients. Patients with pulmonary adenocarcinoma have a particularly poor prognosis if this histological type is combined with high tumour cell C4.4A expression.