Chinese Journal of Lung Cancer (Apr 2008)
Down-regulation of SOCS3 Expression by Methylation Correlates with Lymph Node Metastases of NSCLCs
Abstract
Background and objective It has been proven that suppressor of cytokine signaling 3 (SOCS3) contributes to inhibition of cell overgrowth, induction of apoptosis and stabilization. In the present study, we addressed the SOCS3 expression in non-small cell lung cancer (NSCLC) and explored the relationship between SOCS3 expression and lymph node metastases as well as clinicopathological characteristics in lung cancer patients. Methods Western blotting analysis was used to examine the expression of SOCS3 in 30 NSCLCs and non-tumor tissues. The methylated status of SOCS3 gene was determined by methylation-specific PCR (MSP) assay in the same 30 samples. Immunohistochemical staining was applied to determine SOCS3 expression in 90 NSCLC sections and the correlation of SOCS3 expression with lymph node metastases and clinicopathological characteristics was also analyzed. Results SOCS3 expression was much lower in 30 NSCLCs than tnat in non-tumorous counterparts of the same case (optical density were 26.3±12.3 and 78.4±14.5 respectively, P=0.000) by western blotting analysis. MSP showed that the methylated rate of SOCS3 gene was (20/30) 66.7% in NSCLCs, and (4/30) 13.3% in non-tumors, and SOCS3 expression was negatively correlated with methylation (r=-0.454, P=0.012). Furthermore, SOCS3 expression was observed in non-tumorous epithelial cells by immunohistochemiscal analysis, and the positive rate of SOCS3 expression in 90 NSCLC samples was (41/90) 45.6%. SOCS3 expression rate was lower in NSCLCs with lymph node metastases (35.4%) compared with non-metastatic NSCLCs (57.1%, P=0.039), and in NSCLCs of stage Ⅲ (36.4%) than in stage Ⅰ+Ⅱ (60.0%, P=0.028). SOCS3 expression was not correlated with histological type or differentiation (P>0.05). Conclusion The results of this study suggest that Down-regulation of SOCS3 expression in NSCLC associated with methylation might be correlated with lymph node metastases as well as clinicopathological stage of NSCLCs.
