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

Aging (Albany NY). 2018 Oct 19;10(10):2755-2771. doi: 10.18632/aging.101585.

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.

Keywords: TACC3; chemoradiotherapy; predictor; rectal cancer; sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Digestive System Surgical Procedures* / adverse effects
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • HCT116 Cells
  • Humans
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Radiation Tolerance
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Retrospective Studies
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Microtubule-Associated Proteins
  • TACC3 protein, human