Prognostic significance of E-cadherin and ZEB1 expression in intraductal papillary mucinous neoplasm
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Ye Rim Chang1,2,*, Taesung Park3,*, Sung Hyo Park1, Yong Kang Kim3, Kyoung Bun Lee4, Sun-Whe Kim1 and Jin-Young Jang1
1Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
2Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
3Department of Statistics, Seoul National University College of Natural Sciences, Seoul, Korea
4Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
*These authors contributed equally to this work
Jin-Young Jang, email: [email protected]
Keywords: epithelial-to-mesenchymal transition; intraductal papillary mucinous neoplasm; ZEB1; differentially expressed gene; biomarker
Received: July 19, 2017 Accepted: November 15, 2017 Published: December 07, 2017
There is an urgent need to investigate the genetic changes that occur in intraductal papillary mucinous neoplasm (IPMN), which is a well-known precursor of pancreatic cancer. In this study, gene expression profiling was performed by removing unwanted variation to determine the differentially expressed genes (DEGs) associated with malignant progression of IPMN. Among the identified DEGs, zinc finger E-box binding homeobox 1 (ZEB1) and E-cadherin, a crucial regulator of epithelial-to-mesenchymal transition (EMT), was validated among identified DEGs.
A total of 76 fresh-frozen tissues were used for gene expression profiling and formalin-fixed, paraffin-embedded blocks from 87 patients were obtained for immunohistochemical analysis. Loss of E-cadherin expression (p = 0.023, odd ratio [OR] = 4.923) and expression of ZEB1 in stromal cells (stromal ZEB1, p < 0.001, OR = 26.800) were significantly correlated with degree of dysplasia. The hazard of death was significantly increased in patients with loss of E-cadherin expression (hazard ratio [HR] = 13.718, p = 0.004), expression of epithelial ZEB1 (HR = 19.117, p = 0.001), and stromal ZEB1 (HR = 6.373, p = 0.043).
Based on the results of this study, loss of E-cadherin and expression of stromal ZEB1 are associated with increased risk of malignant progression. Epithelial and stromal ZEB1, as well as E-cadherin may be strong predictors of survival in patients with IPMN. Our finding suggests that these EMT markers may be utilized as potential prognosticators and may be used to improve and personalize treatment of IPMN.
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