Abstract

This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4), a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC) and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3%) expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010). In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

Highlights

  • Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies with a high mortality rate

  • In this study, we examined TBX4 expression in 77 stage II PDAC tumors to determine whether TBX4 expression was associated with survival and other clinicopathological features in this resectable subgroup

  • 48 PDAC cases with a labeling ratio ≥25% were classified as high level of TBX4 expression, wherease those showing a labeling ratio

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Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies with a high mortality rate It is the fourth leading cause of cancer death in the United States, and the sixth leading cause of death from malignant disease in China [1,2]. The long-term survival rate of these PDAC patients is still low (less than 20%), with a median overall survival of 18 to 24 months [3,4]. Some clinicopathological parameters such as tumor size, stage, and lymph node metastasis have been proven to be reproducible prognostic determinants in pancreatic cancer

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