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Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma
Silvia Vanessa Lourenço1, Cláudia Malheiros Coutinho-Camillo, Marcilei Elisa Cavicchioli Buim
1Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil. silvialourenco.70@terra.com.br
Aims:
Claudins, a large family of essential tight junction (TJ) proteins, are abnormally regulated in human carcinomas, especially claudin-7. The aim of this study was to investigate claudin-7 expression and alterations in oral squamous cell carcinoma (OSCC).
Methods And Results:
Expression of claudin-7 was analysed in 132 cases of OSCC organized in a tissue microarray. Claudin-7 mRNA transcript was evaluated using real-time polymerase chain reaction and the methylation status of the promoter was also assessed. Claudin-7 was negative in 58.3% of the cases. Loss of claudin-7 protein expression was associated with recurrence (P = 0.019), tumour size (P = 0.014), clinical stage of OSCC (P = 0.055) and disease-free survival (P = 0.015). Down-regulation of the claudin-7 mRNA transcripts was observed in 78% of the cases, in accordance with immunoexpression. Analysis of the methylation status of the promoter region of claudin-7 revealed that treatment of O28 cells (that did not express claudin-7 mRNA transcripts) with 5-Aza-2'-Deoxycytidine (5-Aza-dC) led to the re-expression of claudin-7 mRNA transcript.
Conclusion:
Loss of claudin-7 expression is associated with important subcellular processes in OSCC with impact on clinical parameters.
Insights
Loss of claudin-7 protein expression is common in oral squamous cell carcinoma (OSCC). This down-regulation correlates with tumor size, stage, and poorer survival, suggesting claudin-7 is a key biomarker in OSCC progression.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Claudins are crucial tight junction proteins frequently dysregulated in human carcinomas.
- Claudin-7, specifically, shows altered expression patterns in various cancers, necessitating further investigation in oral squamous cell carcinoma (OSCC).
Purpose of the Study:
- To investigate the expression status and alterations of claudin-7 in oral squamous cell carcinoma (OSCC).
- To correlate claudin-7 expression with clinical parameters and survival outcomes in OSCC patients.
Main Methods:
- Claudin-7 protein expression was assessed in 132 OSCC tissue microarrays.
- Claudin-7 mRNA transcript levels were quantified using real-time polymerase chain reaction.
- The methylation status of the claudin-7 promoter region was analyzed, with functional studies involving 5-Aza-2'-Deoxycytidine treatment.
Main Results:
- Claudin-7 protein was found to be negative in 58.3% of OSCC cases.
- Loss of claudin-7 expression significantly correlated with increased tumor size, advanced clinical stage, recurrence, and reduced disease-free survival.
- Down-regulation of claudin-7 mRNA was observed in 78% of cases, and promoter methylation was identified as a mechanism for its silencing, reversible with 5-Aza-dC treatment.
Conclusions:
- Loss of claudin-7 expression is a significant finding in OSCC.
- Claudin-7 down-regulation is associated with critical subcellular alterations impacting key clinical parameters in OSCC.
- Claudin-7 may serve as a prognostic biomarker for OSCC.
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