| Introduction Nasopharyngeal carcinoma(NPC) is one of the most common malignancies in Southern China. Although the introduction of intensity-modulated radiation therapy(IMRT) and its combination with chemotherapy have substantially improved the locoregional control, distant metastasis remains as a major cause of treatment failure after the treatment. Latent membrane protein-1(LMP-1) is one of the major transformation-related, Epstein-Barr virus(EBV) encoded genes. It has been identified as encoding an oncoprotein that is thought to be a key modulator in NPC pathogenesis and progression. Compared with the patients with low expression of LMP1, the patients with high expression of it have a higher possibility of metastasis, but the specific mechanism is still not completely clear. Siah1 protein is one of members of the seven in absentia family, and it plays an important role in the development of tumors. Some studies have reported that the expression of Siah1 in tumor tissues is abnormal, and affects the prognosis of patients, but less research on it in NPC patients. It is not clear that if there is a correlation between LMP1 and Siah1.Materials and Methods In this study, there are one hundred and twenty-eight histologically diagnosed non-metastatic NPC patients treated by IMRT included. We use Immunohistochemical staining and tissue microarray(TMA) to know the expression of LMP1 and Siah1. Briefly, we scored the staining intensity as: nostaining(score 0), weak(score 1), moderate(score 2) and strong(score 3). Percentage of positive cells was graded as following: 0–5%(grade 0), 6–25%(grade 1), 26–50%(grade 2), 51-75%(grade 3) and 76-100%(grade 4). The intensity score and the percentage grade were added to obtain a overall positivity index. Finally, we experientially defined overall positivity index 0-3 as negative and ≧4 as positive for LMP1 and Siah1 expression at protein levels.Results Immunohistochemical staining of Siah1 was observed in both the cytoplasm and/or nuclear of tumor cells, and immunohistochemical staining of LMP1 was observed in the membrane and cytoplasm. The medium follow-up time of the whole cohort was 62 months. The 5-year overall survival rate(OS), locoregional relapse-free survival rate(LRRFS), progression-free survival rate(PFS) and distant metastasis-free survival rate(DMFS) were 83.3%, 92.0%, 74.4% and 78.4%, respectively. The DMFS and PFS rate of LMP1(-)group were higher than that of LMP1(+) group(P value were 0.059 and 0.066). The 5-year OS, LRRFS, DMFS and PFS rate of the Siah1(+) group and the Siah1(-) group were 89.1% vs.76.7%(P=0.053), 94.1% vs.89.4%(P=0.353), 85.0% vs.70.6%(P=0.045), 82.1vs.65.5%(P=0.035), respectively. Multivariate analyses indicated that Siah1(+) was the independent progression factor in OS, PFS and DMFS, P value were 0.022, 0.002 and 0.002, respectively. LMP1(+) was the independent progression factor in LRRFS, PFS and DMFS, P value were 0.062, 0.004 and 0.004, respectively. Correlation analysis between the scores of 128 LMP1 and Siah1 after the immunohistochemical staining indicated that the relationship between them was positive correlation(r=0.507, P=0.000)Conclusions Patients with high expression of LMP1 and low expression of Siah1 indicate theworse prognosis.The relationship between LMP1 and Siah1 is positive correlation. The interaction of LMP1 and Siah1 maybe play an important role nasopharyngeal carcinoma. |
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