| Backgrounds:Sine oculis homeobox homolog1(Sâ…¨1) protein is a member of the homeobox transcription factor family. Overexpression of SIX1contributes to cancer progression and is associated with adverse outcomes in various cancer types including breast, ovarian, uterine cervical and liver. However, the expression of Sâ…¨1protein in gastric adenocarcinoma(GAC) is not clear.Object:In this paper we detected the localization of the Sâ…¨1protein in MKN-1and probe into the correlations between the over-expression of Sâ…¨1protein and clinical pathological parameters and prognosis in GAC.Material and Methods:Localization of the Sâ…¨1protein was determined in MKN-1, a gastric cancer cell line, using immunofluorescence (IF) staining and si-Sâ…¨1transfection. Sâ…¨1mRNA level was detected in12pairs fresh tissues of GAC and normal gastric mucosa using quantitative real-time polymerase chain reaction (qRT-PCR), and Sâ…¨1protein expression was assessed in163GAC,35gastric dysplasia and26normal gastric mucosa using immunohistochemical (IHC) staining. Relativity of Sâ…¨1protein expression and pathological parameters of GAC were analyzed using Chi-square tests. Survival rates were calculated using the Kaplan-Meier method, and differences in survival curves were analyzed using log-rank tests. Multivariate survival analysis was performed using the Cox proportional hazards regression model. Sâ…¨1protein showed a mainly cytoplasmic staining pattern in GAC using IF and IHC staining.Results:The positive Sâ…¨1protein expression rate was80.4%(131/163) in GAC, which was significantly lower both in gastric dysplasia (45.7%,16/35) and normal gastric mucosa (26.9%,7/26)(P<0.01). Similarly, the strongly positive Sâ…¨1protein expression rate was also higher in gastric cancer tissues (63.2%,103/163) compared with tissues with gastric dysplasia (20.0%,7/35) or normal gastric mucosa (11.5%,3/26)(P<0.01). The strongly positive Sâ…¨1protein expression rate was significantly correlated with tumor size, clinical stage, lymph node metastasis and serosal invasion of GAC (P<0.01or P<0.05), while there was no association with gender, age, tumor size, Lauren classification or histological types of GAC. qRT-PCR data also confirmed increased levels of Sâ…¨1mRNA expression in GAC compared with the normal gastric mucosa in fresh tissues. In addition, the strongly positive signals were frequently observed in tumor blood vessels and/or lymphatic vessels. GAC patients with high expression of the Sâ…¨1had shorter overall and disease-free survival rates than those with low Sâ…¨1protein expression (P<0.001). Furthermore, using multivariate analysis, the abnormal expression of Sâ…¨1protein was discovered to be an independent hazard for survival in patients with GAC along with clinical stage and serosal invasion (P<0.001).Conclusions:Sâ…¨l protein was frequently upregulated in GAC and its expression status may be an independent biomarker for prognostic evaluation of GAC. |
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