1994

ELAVL1

ELAV like RNA binding protein 1;ELAVL1;ELAV like RNA binding protein 1

ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R)|ELAV-like protein 1|Hu antigen R|embryonic lethal, abnormal vision, drosophila, homolog-like 1|hu-antigen R

19p13.2

protein-coding

BACKGROUND: The role of human antigen R (HuR) and its prognostic value in breast cancer is currently only partially understood. This study aimed to determine the levels of expression of HuR in breast cancer and assess its prognostic value. MATERIALS AND METHODS: HuR expression levels were assessed in a cohort of human breast cancer specimens and cell lines using both quantitative and qualitative analysis along with immunohistochemical techniques and the results were compared to the patient details. RESULTS: Immunohistochemical staining revealed a weak HuR staining pattern in breast tumour sections compared to the intense epithelial staining of the normal breast tissues. The levels of HuR transcripts were lower in the more advanced TNM4 and TNM3, poor outcome NPI-2 (Nottingham Prognostic Index) and NPI-3 and node-positive tumours compared with the early stage TNM2 and TNM1, NPI-1, and node-negative tumours, although these values did not reach statistical significance. The patients with metastasis, those who died of breast cancer and those with bone metastasis had significantly decreased levels of HuR transcripts, (p=0.031, p=0.018 or p=0.038 respectively) compared to the disease-free patients. The patients with poor prognosis, including those with metastasis and those who died of breast cancer, had a significantly lower level of HuR transcripts compared to the disease-free patients (p=0.021). High levels of HuR correlated with longer overall survival, although the values did not reach statistical significance (p=0.06). CONCLUSION: While no significant association of the levels of HuR expression with pathological status of breast cancer is reported, HuR may represent a prognostic factor in human breast cancer, as patients expressing high levels of HuR have a favourable prognosis, and the prognostic role of HuR for breast cancer metastasis, particularly bone metastasis is supported.

Esophageal squamous cell carcinoma (ESCC) is one of the most frequent cancers and a leading cause of death from cancer in China. The human ELAV-like protein HuR has been found to contribute to cancer development and progression through stabilizing a group of cellular mRNAs of cancer-related genes. In this study, we investigated the expression of HuR in a cohort of ESCC patients using immunohistochemical staining. HuR detected in the cytoplasm of cancer cells was positive in 46.6% of 58 ESCC specimens; 75.9% of these specimens had nuclear immunoreactivity for HuR. Cytoplasmic HuR expression was higher in cancer tissues compared to 20 matched adjacent noncancerous tissues. A clinicopathological study showed that cytoplasmic HuR expression was positively associated with lymph node metastasis, depth of tumor invasion, and advanced stage, whereas nuclear HuR expression was not correlated with any clinicopathological factors. Patients positive for cytoplasmic HuR expression had a cumulative 5-year survival rate of 25.3%, whereas it was 43.8% for patients negative for cytoplasmic HuR expression. In a multivariate analysis, cytoplasmic HuR expression was an independent prognostic factor, whereas nuclear positivity for HuR was not. Our results indicate that high cytoplasmic HuR expression is associated with positive lymph node metastasis, deep tumor invasion, high stage, and poor survival in ESCC. Thus, HuR is the first mRNA stability protein whose expression is associated with poor survival in esophageal cancer.

The expression levels of the RNA-binding protein Hu antigen (HuR) and vascular endothelial growth factor-C (VEGF-C) were examined immunohistochemically in 81 non-small cell lung cancers (NSCLC) and 15 benign human lung tissues. HuR showed a nuclear overexpression in 82.7% (67/81) of NSCLC specimens. Cytoplasmic immunoreactivity for HuR was observed in 45.7% (37/81) of NSCLC, while only nuclear expression of HuR was observed in 13.3% (2/15) of benign lung tissues. The expression of VEGF-C was present in a subgroup of 70.4% (57/81) of tumor cases. In the human NSCLC samples, cytoplasmic but not nuclear HuR expression was significantly associated with increased levels of VEGF-C and with clinicopathological variables, including high tumor grade, poor differentiation and lymph node metastasis. In vitro, HuR showed a predominantly nuclear staining in Lewis lung cancer cells, as seen by confocal microscopy. When lung cancer cells were treated with siRNA targeted against HuR, expression levels of the HuR and VEGF-C proteins were significantly reduced, as seen by Western blotting. Our findings indicate that there is a dysregulation of the cellular distribution of the mRNA stability factor HuR in a subset of NSCLC. Examination of cytoplasmic HuR in NSCLC tissues will allow for valuable prognostic diagnosis of lymph node metastasis, as HuR might be an important mediator regulating the expression of VEGF-C.