[Down-regulation of SOCS3 expression by methylation correlates with lymph node metastases of NSCLCs.]
Siyang Zhang1, Qingfu Zhang, Yumei Gu
1Department of Pathology, China Medical University, Shenyang, Liaoning 110001, China.
Background:
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).
Conclusions:
The results of this study suggest that Downregulation of SOCS3 expression in NSCLC associated with methylation might be correlated with lymph node metastases as well as clinicopathological stage of NSCLCs.
Insights
Suppressor of cytokine signaling 3 (SOCS3) is downregulated in non-small cell lung cancer (NSCLC), linked to gene methylation. Lower SOCS3 expression correlates with lymph node metastasis and advanced NSCLC stages.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Context:
- Suppressor of cytokine signaling 3 (SOCS3) plays a role in inhibiting cell overgrowth and inducing apoptosis.
- SOCS3 expression and its clinical significance in non-small cell lung cancer (NSCLC) remain to be fully elucidated.
Purpose:
- To investigate SOCS3 expression levels in NSCLC tissues.
- To explore the correlation between SOCS3 expression, gene methylation, lymph node metastasis, and clinicopathological characteristics in NSCLC patients.
Summary:
- Western blotting and immunohistochemistry revealed significantly lower SOCS3 expression in NSCLC tissues compared to non-tumor tissues.
- Methylation-specific PCR showed a higher methylation rate of the SOCS3 gene in NSCLC, negatively correlating with SOCS3 expression.
- Reduced SOCS3 expression was associated with lymph node metastasis and advanced clinical stages (III vs. I+II) in NSCLC.
Impact:
- This study suggests that SOCS3 downregulation, potentially due to methylation, is a relevant factor in NSCLC progression and metastasis.
- Findings highlight SOCS3 as a potential biomarker for NSCLC lymph node metastasis and clinical staging.
- Understanding the role of SOCS3 in NSCLC could inform future therapeutic strategies targeting lung cancer development.
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