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   <subfield code="a">Low Expression of Claudin-4 is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[Chang Sung, Song Han, Seok-Hyung Kim]</subfield>
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   <subfield code="a">Background: Claudins are 22-27kDa sized adhesion molecules that constitute tight junctions. Their expression levels are often tissue-specific, and their altered degrees of expression have been reported in a variety of cancers. In addition, the prognostic significance of claudin expression has been implicated in various human cancers. However, the prognostic significance of claudin-4 expression in esophageal squamous cell carcinoma (ESCC) remains to be clarified. Materials and Methods: We investigated the prognostic significance of claudin-4 expression in 164 cases of ESCC using immunohistochemisty. We also evaluated claudin-4 mRNA expression levels using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) and analyzed its specific promoter methylation status using quantitative methylation-specific PCR. Results: According to clinicopathological parameters, low claudin-4 expression was found to be significantly associated with histological differentiation (P=0.003), invasion depth (P=0.002), and lymph node metastasis (P=0.024). Low claudin-4 expression showed unfavorable influences on disease-free survival (P=0.0115) and overall survival (OS) (P=0.0009). In multivariate analysis, low claudin-4 expression was an independent predictor of poor OS (P=0.007). Claudin-4 mRNA levels assessed using real-time RT-PCR were consistent with the protein levels determined using immunohistochemistry. Furthermore, this study demonstrates that loss of claudin-4 is associated with promoter hypermethylation. Conclusions: Our study indicates that claudin-4 expression is deregulated in ESCC, implying its potential use as a prognostic biomarker in ESCC.</subfield>
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