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Published on: July 20, 2014
Upregulated TC1 and downregulated Chibby were correlated with the aberrant β-catenin expression in laryngeal squamous
Gang Ren1, Bingliang Ma1, Jianqiu Wang1
1Department of Otolaryngology, the First People's Hospital of Huzhou, the First affiliated Hospital of Huzhou university, Huzhou, Zhejiang, China.
Abstract:
As an important member of Wnt/β-catenin signaling pathway, the aberrant expression of β-catenin has been implicated in many cancers. Chibby, a β-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the β-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and β-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, β-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of β-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of β-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of β-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of β-catenin in LSCC was 96.00% in TC1+/Chibby-, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby-, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby-, TC1+/Chibby+, TC1-/Chibby-, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and β-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of β-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.
Insights
Thyroid cancer 1 (TC1) upregulation and Chibby downregulation correlate with aberrant beta-catenin expression in laryngeal squamous cell carcinoma (LSCC). These changes are linked to increased Cyclin D1 and MMP-7, but not overall survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant beta-catenin expression is implicated in various cancers, playing a key role in the Wnt/beta-catenin signaling pathway.
- Chibby acts as an antagonist in this pathway, while thyroid cancer 1 (TC1) is an activator that can relieve Chibby's inhibitory effects.
- TC1 is frequently overexpressed in human tumors, suggesting its potential role in cancer development.
Purpose of the Study:
- To investigate the expression levels of TC1, Chibby, and beta-catenin in laryngeal squamous cell carcinoma (LSCC).
- To explore the associations among TC1, Chibby, and beta-catenin expression in LSCC.
- To examine the correlation of these proteins with clinicopathological features and downstream targets like c-Myc, Cyclin D1, and MMP-7 in LSCC.
Main Methods:
- Immunohistochemistry was employed to assess the expression of TC1, Chibby, beta-catenin, c-Myc, Cyclin D1, and MMP-7 in 53 LSCC patient samples.
- Expression levels were compared between LSCC tissues and normal laryngeal squamous epithelium (NLSE).
- Statistical analyses were performed to correlate protein expression with clinicopathological parameters and patient survival.
Main Results:
- LSCC tissues exhibited upregulated TC1, downregulated Chibby, and aberrant cytoplasmic beta-catenin compared to NLSE (P < .001).
- High TC1 expression correlated with advanced tumor site, TNM and T stage, lymphovascular invasion, and poor differentiation (P < .050).
- Aberrant beta-catenin expression was associated with tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation (P < .050).
- Upregulated TC1 and downregulated Chibby were significantly correlated with aberrant beta-catenin expression (P < .001).
- High expression of Cyclin D1 and MMP-7 was observed in LSCC tissues and correlated with TC1/Chibby expression patterns (P < .001).
- No significant association was found between the expression of TC1, Chibby, beta-catenin, and overall patient survival (P > .05).
Conclusions:
- TC1 upregulation and Chibby downregulation are associated with aberrant beta-catenin signaling in LSCC.
- These molecular changes correlate with aggressive clinicopathological features and elevated expression of Cyclin D1 and MMP-7.
- The study suggests a role for the TC1/Chibby/beta-catenin axis in LSCC progression, independent of overall survival.
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