Research Paper Volume 10, Issue 10 pp 2755—2771

Pretreatment TACC3 expression in locally advanced rectal cancer decreases the response to neoadjuvant chemoradiotherapy

Wen-juan Ma 1, 3, 4, *, , Yang-kui Gu 1, 3, 6, *, , Jian-hong Peng 1, 2, 3, *, , Xue-cen Wang 1, 3, , Xin Yue 1, 3, , Zhi-zhong Pan 1, 2, 3, , Gong Chen 1, 2, 3, , Hai-neng Xu 7, , Zhong-guo Zhou 1, 3, 5, , Rong-xin Zhang 1, 2, 3, ,

  • 1 State Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong, P.R. China
  • 2 Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
  • 3 Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, P.R. China
  • 4 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
  • 5 Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
  • 6 Microinvasive Interventional Department, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
  • 7 Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA
* Equal contribution

received: July 27, 2018 ; accepted: September 26, 2018 ; published: October 19, 2018 ;

https://doi.org/10.18632/aging.101585
How to Cite

Copyright: Ma et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Chemoradiotherapy combined with surgical resection is the standard treatment for locally advanced rectal cancer, but not all the patients respond to neoadjuvant treatment. Transforming acidic coiled-coil protein-3 (TACC3) is frequently aberrantly expressed in rectal cancer tissue. In this study, we investigated whether TACC3 could serve as a biomarker predictive of the efficacy of chemoradiotherapy. In all, 152 rectal cancer patients with tumor tissue collected at biopsy and set aside before treatment were enrolled in this study. All patients received chemoradiotherapy and surgical resection. Immunohistochemically detected tumoral TACC3 expression significantly decreased sensitivity to chemoradiotherapy [risk ratio (RR) = 2.236, 95% confidence interval (CI): 1.447–3.456; P = 0.001] and thus the pathological complete response rate (P = 0.001). TACC3 knockdown using specific siRNA enhanced radiotherapy-induced decreases in proliferation and colony formation by HCT116 and SW480 cells and increased the incidence of radiotherapy-induced apoptosis. Cox multivariate analysis showed that TACC3 was a significant prognostic factor for overall survival (P = 0.017) and disease-free survival (P = 0.020). These findings suggest TACC3 expression may be predictive of chemoradiotherapy sensitivity and prognosis in locally advanced rectal cancer.

Abbreviations

TACC3: Transforming acidic coiled-coil protein-3; LARC: locally advanced rectal cancer; CRT: chemoradiotherapy; TME: total mesorectal excision; MRI: magnetic resonance imaging; GBM: Glioblastoma multiforme; EMT: the epithelial–mesenchymal transition; pCR: pathological complete response; PNI: perineural invasion; CI: confidence interval; RR: risk ratio; TDs: tumor deposits; TRG: tumor regression grading; CRC: colorectal cancer; NCCN: The National Comprehensive Cancer Network; ESMO: The European Society for medical oncology; AJCC: The American Joint Committee on Cancer; SP: streptavidin peroxidase; IHC: immunohistochemistry.