Brief Article
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World J Gastroenterol. Oct 28, 2013; 19(40): 6876-6882
Published online Oct 28, 2013. doi: 10.3748/wjg.v19.i40.6876
Overexpression of nuclear β-catenin in rectal adenocarcinoma is associated with radioresistance
Lin Wang, Xiao-Mei Zhang, Zhen Li, Xi-Jun Liu, Jie Chai, Guang-Yong Zhang, Yu-Feng Cheng
Lin Wang, Xiao-Mei Zhang, Zhen Li, Yu-Feng Cheng, Department of Radiation Oncology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Xi-Jun Liu, Department of Radiation Oncology, Shandong Tumor Hospital and Institute, Jinan 250117, Shandong Province, China
Jie Chai, Department of General Surgery, Shandong Tumor Hospital and Institute, Jinan 250117, Shandong Province, China
Guang-Yong Zhang, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Chai J and Zhang GY collected all the human material; Wang L, Zhang XM, Li Z and Liu XJ performed the majority of experiments; Wang L and Cheng YF designed the study and wrote the manuscript.
Supported by Natural Science Foundation of Shandong Province, China, No. ZR2012HQ032; and China Postdoctoral Science Foundation funded project, No. 2013M531614
Correspondence to: Yu-Feng Cheng, MD, Department of Radiation Oncology, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China. 33943219@qq.com
Telephone: +86-531-82169441 Fax: +86-531-82169441
Received: June 14, 2013
Revised: July 29, 2013
Accepted: September 16, 2013
Published online: October 28, 2013
Processing time: 151 Days and 17.9 Hours
Abstract

AIM: To investigate the association between nuclear β-catenin overexpression in rectal adenocarcinoma and radioresistance.

METHODS: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of β-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of β-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between β-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance.

RESULTS: Nuclear β-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear β-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane β-catenin was expressed in favor of good TRG (≥ 3). Nuclear β-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear β-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear β-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear β-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity.

CONCLUSION: Nuclear β-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.

Keywords: β-catenin; Rectal cancer; Preoperative radiotherapy; Radioresistance; Colorectal cancer

Core tip: In this paper we investigated the relationship between overexpression of nuclear β-catenin in rectal adenocarcinoma and radioresistance. We first confirmed that nuclear β-catenin overexpression in rectal adenocarcinoma is associated with radioresistance. Most importantly, we found that nuclear β-catenin-based prediction achieved a 83% accuracy, 65% sensitivity and 88% specificity for radioresistance. We provided a novel possible molecular mechanism to explain the radioresistance in rectal adenocarcinoma and thus may provide a new therapeutic target for enhancing radiosensitivity.