Low Expression of Claudin-4 is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma
Autor: | Seok-Hyung Kim, Song Yiang Han, Chang Ohk Sung |
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Rok vydání: | 2010 |
Předmět: |
Male
Pathology medicine.medical_specialty Poor prognosis Esophageal Neoplasms endocrine system diseases Ovarian cancer cell line urologic and male genital diseases Esophageal squamous cell carcinoma Immunoenzyme Techniques Esophagus Surgical oncology Biomarkers Tumor medicine Humans Neoplasm Invasiveness RNA Messenger Claudin-4 Promoter Regions Genetic Claudin Aged Neoplasm Staging Tight junction Reverse Transcriptase Polymerase Chain Reaction business.industry Cell adhesion molecule Membrane Proteins DNA Neoplasm DNA Methylation Esophageal cancer Prognosis medicine.disease digestive system diseases Survival Rate Oncology Tissue Array Analysis Lymphatic Metastasis Carcinoma Squamous Cell Female Surgery business Microdissection |
Zdroj: | Annals of Surgical Oncology. 18:273-281 |
ISSN: | 1534-4681 1068-9265 |
Popis: | Claudins are 22-27 kDa 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.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.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.Our study indicates that claudin-4 expression is deregulated in ESCC, implying its potential use as a prognostic biomarker in ESCC. |
Databáze: | OpenAIRE |
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