title: Overexpression of nuclear β-catenin in rectal adenocarcinoma is associated with radioresistance.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Nuclear β-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.
authors.affiliation: Lin Wang, Xiao-Mei Zhang, Zhen Li, Yu-Feng Cheng, Department of Radiation Oncology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Chai
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Zhang
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D016009:Chi-Square Distribution; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D016017:Odds Ratio; D011836:Radiation Tolerance; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: Colorectal cancer; Preoperative radiotherapy; Radioresistance; Rectal cancer; β-catenin