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核β-连环蛋白在直肠腺癌中的过表达与放射抵抗有关。

Overexpression of nuclear β-catenin in rectal adenocarcinoma is associated with radioresistance.

机构信息

Lin Wang, Xiao-Mei Zhang, Zhen Li, Yu-Feng Cheng, Department of Radiation Oncology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China.

出版信息

World J Gastroenterol. 2013 Oct 28;19(40):6876-82. doi: 10.3748/wjg.v19.i40.6876.

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.

摘要

目的

探讨直肠腺癌中核β-连环蛋白(β-catenin)过度表达与放射抵抗之间的关系。

方法

进行回顾性分析。分析涉及 136 例局部晚期直肠腺癌患者,这些患者接受了短程术前放疗和根治性切除术。通过免疫组织化学方法检测预处理活检标本和切除的原发性肿瘤组织中β-catenin 的表达。使用肿瘤退缩分级(TRG)系统评估β-catenin表达与放射抵抗的相关性。还分析了β-catenin表达与临床病理特征之间的关系。采用单变量和逻辑多变量回归分析确定放射抵抗的独立因素。

结果

与放射敏感的直肠腺癌相比,放射抵抗的直肠腺癌中核β-catenin 过度表达更为明显(57.6%比 16.7%,P < 0.001)。核β-catenin 过度表达有利于较差的 TRG(≤2),而膜β-catenin 表达有利于较好的 TRG(≥3)。肿瘤细胞分化(P = 0.018)、淋巴结转移(P = 0.022)和 TRG(P < 0.001)中β-catenin 的核表达存在显著差异。单变量分析表明,放射抵抗与核β-catenin 过度表达有关(P < 0.001)。此外,逻辑多变量回归分析表明,只有三个因素与放射抵抗有关,即肿瘤大小(P < 0.001)、肿瘤细胞分化(P < 0.001)和核β-catenin 过度表达(P < 0.001)。单独使用放射抵抗作为预测靶点,基于核β-catenin 的预测准确率为 83%,敏感度为 65%,特异度为 88%。

结论

核β-catenin 过度表达可能是预测直肠腺癌对术前放疗反应的有价值的候选标志物。

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