Overexpression of Nuclear β-catenin in Rectal Adenocarcinoma is Associated with Radioresistance

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2013 Nov 5

PMID 24187464

Citations 11

Authors

Lin Wang

Xiao-Mei Zhang

Zhen Li

Xi-Jun Liu

Jie Chai

Guang-Yong Zhang

Yu-Feng Cheng

Affiliations

Soon will be listed here.

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.

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References

Zhang B, Ougolkov A, Yamashita K, Takahashi Y, Mai M, Minamoto T . beta-Catenin and ras oncogenes detect most human colorectal cancer. Clin Cancer Res. 2003; 9(8):3073-9. View

Chen M, Woodward W, Behbod F, Peddibhotla S, Alfaro M, Buchholz T . Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line. J Cell Sci. 2007; 120(Pt 3):468-77. DOI: 10.1242/jcs.03348. View

Shinto E, Hashiguchi Y, Ueno H, Kobayashi H, Ishiguro M, Mochizuki H . Pretreatment CD133 and cyclooxygenase-2 expression as the predictive markers of the pathological effect of chemoradiotherapy in rectal cancer patients. Dis Colon Rectum. 2011; 54(9):1098-106. DOI: 10.1097/DCR.0b013e3182218155. View

Pacelli F, Sanchez A, Covino M, Tortorelli A, Bossola M, Valentini V . Improved outcomes for rectal cancer in the era of preoperative chemoradiation and tailored mesorectal excision: a series of 338 consecutive cases. Am Surg. 2013; 79(2):151-61. View

Moussata D, Amara S, Siddeek B, Decaussin M, Hehlgans S, Paul-Bellon R . XIAP as a radioresistance factor and prognostic marker for radiotherapy in human rectal adenocarcinoma. Am J Pathol. 2012; 181(4):1271-8. DOI: 10.1016/j.ajpath.2012.06.029. View

Harris T, Peifer M . Decisions, decisions: beta-catenin chooses between adhesion and transcription. Trends Cell Biol. 2005; 15(5):234-7. DOI: 10.1016/j.tcb.2005.03.002. View

Lim S, Yu C, Hong Y, Kim T, Kim J, Kim J . Long-term outcomes in patients with locally advanced rectal cancer treated with preoperative chemoradiation followed by curative surgical resection. J Surg Oncol. 2012; 106(6):659-66. DOI: 10.1002/jso.23181. View

Watson R, Spalding A, Zielske S, Morgan M, Kim A, Bommer G . GSK3beta and beta-catenin modulate radiation cytotoxicity in pancreatic cancer. Neoplasia. 2010; 12(5):357-65. PMC: 2864473. DOI: 10.1593/neo.92112. View

Woodward W, Chen M, Behbod F, Alfaro M, Buchholz T, Rosen J . WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci U S A. 2007; 104(2):618-23. PMC: 1766434. DOI: 10.1073/pnas.0606599104. View

10.

Dworak O, Keilholz L, Hoffmann A . Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997; 12(1):19-23. DOI: 10.1007/s003840050072. View

11.

Horst D, Reu S, Kriegl L, Engel J, Kirchner T, Jung A . The intratumoral distribution of nuclear beta-catenin is a prognostic marker in colon cancer. Cancer. 2009; 115(10):2063-70. DOI: 10.1002/cncr.24254. View

12.

Wang Y, Liu L, Zhou D . Inhibition of p38 MAPK attenuates ionizing radiation-induced hematopoietic cell senescence and residual bone marrow injury. Radiat Res. 2011; 176(6):743-52. PMC: 3390189. DOI: 10.1667/rr2727.1. View

13.

Kuremsky J, Tepper J, McLeod H . Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2009; 74(3):673-88. DOI: 10.1016/j.ijrobp.2009.03.003. View

14.

Bujko K, Richter P, Smith F, Polkowski W, Szczepkowski M, Rutkowski A . Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: a prospective multicentre study. Radiother Oncol. 2013; 106(2):198-205. DOI: 10.1016/j.radonc.2012.12.005. View

15.

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R . Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004; 351(17):1731-40. DOI: 10.1056/NEJMoa040694. View

16.

Ho S, Wu W, Chiu H, Chen Y, Ho Y, Guo H . Arsenic trioxide and radiation enhance apoptotic effects in HL-60 cells through increased ROS generation and regulation of JNK and p38 MAPK signaling pathways. Chem Biol Interact. 2011; 193(2):162-71. DOI: 10.1016/j.cbi.2011.06.007. View

17.

Qiu J, Yang G, Shen Z, Xie Y, Wang L . hPEBP4 as a predictive marker for the pathological response of rectal cancer to preoperative radiotherapy. Int J Colorectal Dis. 2012; 28(2):241-6. DOI: 10.1007/s00384-012-1534-3. View

18.

Baldus S, Monig S, Huxel S, Landsberg S, Hanisch F, Engelmann K . MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res. 2004; 10(8):2790-6. DOI: 10.1158/1078-0432.ccr-03-0163. View

19.

Kim K, Chie E, Wu H, Kim S, Lee S, Kang G . High survivin expression as a predictor of poor response to preoperative chemoradiotherapy in locally advanced rectal cancer. Int J Colorectal Dis. 2011; 26(8):1019-23. DOI: 10.1007/s00384-011-1180-1. View

20.

van Es J, Barker N, Clevers H . You Wnt some, you lose some: oncogenes in the Wnt signaling pathway. Curr Opin Genet Dev. 2003; 13(1):28-33. DOI: 10.1016/s0959-437x(02)00012-6. View