Abstract

Gene mutation and pathogenesis bacteria are highly associated with colorectal cancer (CRC) development and progression. Autophagy is a self-clearance pathway to degrade abnormal proteins and infected bacteria in cells. Autophagy plays a dual role in cancer development. Among the autophagy-related (ATG) proteins, ATG5 is the key component required for the core machinery of autophagy. However, the role of ATG5 in CRC malignancy remains unclear. Herein, we found that a high ATG5 protein level was correlated with poor overall survival (OS) and disease-free survival (DFS) of 118 patients with CRC. After stratification with demographic and clinicopathologic factors, a high ATG5 protein level was significantly correlated with unfavorable overall survival in female and elder (>60 year) CRC patients and tumor tissues with poor differentiation, late T stages (III + IV), whereas the ATG5 protein level was positively associated with the overall survival in CRC patients without lymph node invasion and radiation therapy. In contrast, a high ATG5 protein level was significantly associated with worse DFS in CRC patients with early stage of AJCC and no radiation therapy. In addition, colorectal cancer cells stably harboring small interfering RNA (siRNA) against ATG5 diminished the tumorsphere formation and sensitized cancer cells to chemotherapeutic agents. Taken together, our results suggest that ATG5 might be a prognostic biomarker for CRC and a potential therapeutic target for CRC patients.

Highlights

  • Colorectal cancer (CRC) is the top three leading cause of cancer death in both men and women worldwide, in developed countries [1]

  • The expression of ATG5 was initially verified with IHC staining in tumor tissues of CRC patients

  • The scores for protein levels were categorized into four groups according to the staining intensity (0, no signal; 1, mild; 2, moderate; and 3, strong) and percentage of positive staining (0–100%)

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Summary

Introduction

Colorectal cancer (CRC) is the top three leading cause of cancer death in both men and women worldwide, in developed countries [1]. CRC cancer related mortality has been increased by almost 50% in over the past 50 years and an over 10% mortality increase is expected by 2030, resulting in more than 13 million deaths worldwide [2]. Autophagy is a cellular pathway that reacts under environmental stimulus to maintain homeostasis by degrading abnormal cytoplasmic components including pathogenesis bacteria, organelles, lipids, and proteins [5,6]. These cellular components are digested by lysosomal lytic enzymes for recycling these abnormal components during autophagy [5]

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