Cytoplasmic HuR expression correlates with angiogenesis, lymphangiogenesis, and poor outcome in lung cancer

HuR is a ubiquitously expressed RNA-binding protein that stabilizes the mRNAs of certain genes and regulates the translation to proteins. Elevated cytoplasmic expression of HuR has been suggested to be associated with reduced survival in a wide variety of human carcinomas. However, the clinical significance of HuR expression in lung cancer remains unknown. In this study, we examined HuR expression in 132 patients with non-small cell lung carcinoma (NSCLC) by means of immunohistochemistry and correlated clinicopathologic data, lymphatic microvessel density (LVD), or microvessel density (MVD) with HuR immunostaining. HuR was expressed in 80.3% (106/132) of cases and was predominantly localized in the nucleus. Cytoplasmic HuR expression occurred in 40.9% (54/132) of NSCLC specimens and was associated with high MVD and LVD. In univariate analysis, cytoplasmic HuR, but not nuclear HuR expression was found to significantly influence the relapse-free survival and overall survival. In addition, cytoplasmic expression of HuR was identified as an independent prognostic factor for survival in multivariate analysis. Our data provide evidence for a clinically prognostic role of HuR in NSCLC and demonstrate an association between HuR expression, and angiogenesis and lymphangiogenesis.