Role of autophagy-related protein expression in patients with rectal cancer treated with neoadjuvant chemoradiotherapy

BMC Cancer. 2016 Mar 10:16:207. doi: 10.1186/s12885-016-2250-0.

Abstract

Background: Autophagy, a cellular degradation process, has complex roles in tumourigenesis and resistance to cancer treatment in humans. The aim of this study was to explore the expression levels of autophagy-related proteins in patients with rectal cancer and evaluate their clinical role in the neoadjuvant chemoradiotherapy setting.

Methods: All specimens evaluated were obtained from 101 patients with colorectal cancer who had undergone neoadjuvant chemoradiotherapy and curative surgery. The primary outcomes measured were the expression levels of two autophagy-related proteins (microtubule-associated protein 1 light chain 3 beta (LC3β) and beclin-1) by immunohistochemistry and their association with clinicopathological parameters and patient survival.

Results: Among the 101 patients, the frequency of high expression of beclin-1 was 31.7% (32/101) and that of LC3β was 46.5% (47/101). A pathologic complete response was inversely associated with LC3β expression (P = 0.003) and alterations in the expression of autophagy-related proteins (P = 0.046). In the multivariate analysis, however, autophagy-related protein expression did not show prognostic significance for relapse-free survival or overall survival.

Conclusions: High expression of autophagy-related proteins shows a strong negative association with the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer. Autophagy has clear implications as a therapeutic target with which to improve the efficacy of neoadjuvant chemoradiotherapy.

Keywords: Autophagy; Beclin-1; LC3β; Neoadjuvant chemoradiotherapy; Prognosis; Rectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autophagy / drug effects
  • Autophagy / genetics
  • Autophagy / radiation effects
  • Autophagy-Related Proteins / biosynthesis
  • Autophagy-Related Proteins / genetics
  • Beclin-1 / biosynthesis*
  • Beclin-1 / genetics
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Chemoradiotherapy
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Male
  • Microtubule-Associated Proteins / biosynthesis*
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / radiotherapy*
  • Prognosis
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*

Substances

  • Autophagy-Related Proteins
  • Beclin-1
  • Biomarkers, Tumor
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins