Abstract

BackgroundExpression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors.MethodsWe examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival. The WRAP53 protein was examined by immunohistochemistry in normal mucosa, primary tumors and lymph node metastases from 143 rectal cancer patients participated in a Swedish clinical trial of preoperative radiotherapy.ResultsFrequency of WRAP53 protein expression was increased in primary rectal cancer compared to the normal mucosa (p < 0.05). In non-radiotherapy group positive WRAP53 in primary tumors (p = 0.03, RR, 3.73, 95% CI, 1.13-11.89) or metastases (p = 0.01, RR, 4.11, 95% CI, 1.25-13.14), was associated with poor prognosis independently of stages and differentiations. In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival (p = 0.04). An interaction analysis showed that the correlations of WRAP53 with the prognostic significance with and without radiotherapy in the metastasis differed (p = 0.01). In the radiotherapy group, expression of WRAP53 in metastases gave a better outcome (p = 0.02, RR, 0.32, 95% CI, 0.13-0.84), and an interaction analysis showed significance between the two groups (p = 0.01).ConclusionWRAP53 may be a new biomarker used to predict prognosis and to select suitable patients for preoperative radiotherapy.

Highlights

  • Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors

  • We examined WRAP53 protein in biopsies, and surgical specimens from distant normal mucosa, adjacent normal mucosa, primary tumor and lymph node metastasis from the patients participated in a Swedish rectal cancer clinical trial of preoperative radiotherapy (Uppsala, 1986-11-17, Dnr. 86151) [4]

  • The 143 rectal cancer samples were divided into two groups; tumors not treated with radiotherapy (n = 78) and tumors treated with radiotherapy (n = 65) in order to analyze the role of WRAP53 in the two groups

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Summary

Introduction

Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors. Colorectal cancer is one of the most common types of cancer worldwide [1], and 50% of the patients still develop local or distant recurrence, and eventually die from colorectal cancer despite surgery [2]. Preoperative radiotherapy has been proven to reduce local recurrence and further improve overall survival in rectal cancer. WRAP53 encodes a protein for maintenance of nuclear organelles called Cajal bodies [8,9,10]. WRAP53 protein has been found overexpressed in a broad range of human cancer cell lines in comparison to non-transformed cells. The WRAP53 overexpression promotes cellular transformation, whereas

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