Clinicopathological Association of Autophagy Related 5 Protein with Prognosis of Colorectal Cancer

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.

Bruceine D restrains colorectal cancer tumorigenesis and autophagy by downregulating circ_0068464

“…A set of reports have shown the oncogene role of ATG5 in several cancers, such as prostate cancer (Zhang et al., 2019) and lung adenocarcinoma (He et al., 2020). In addition, ATG5 was correlated with disease‐free survival of CRC patients (Hu & Yang, 2021). Also, ATG5 knockdown lessened the SMAD1‐induced CRC cell migration and proliferation (Zhou et al., 2021).…”

Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer

“…Our cell culture model indicates that autophagy inhibition sensitizes breast cancer cells to chemotherapeutic drugs, leading to better survival in IDC patients. Nevertheless, autophagic flux can be measured only in cell cultures and animal models [ 46 ], not in clinical patients [ 4 , 47 ]. Moreover, lysosomal enzyme defects may result in pseudo-autophagy [ 48 ].…”

“…Moreover, autophagy serves as a “double-edged sword” with opposite functions in tumor initiation and malignancy [ 3 ]. Most studies have indicated that autophagy activation is implicated in tumor progression [ 3 , 4 ]. Thus, autophagy could be a therapeutic target in cancer [ 5 ].…”

Deconvoluting the complexity of autophagy in colorectal cancer: From crucial pathways to targeted therapies

“…There are two important ubiquitination modifications in phagophore elongation and maturation, one of which is that ATG5, ATG12 and ATG16L1 are catalyzed by ATG7 and ATG10 to form a complex and localize to the autophagosome membrane ( 25 ). In CRC, patients with high ATG5 expression generally have a poorer prognosis and are more likely to cause tumor recurrence ( 26 ). Interestingly, the ATG16L1 T300A variant elicits a defect of autophagy, which is closely associated with better patient prognosis ( 27 ).…”