Expression of autophagy-related proteins ATG5 and FIP200 predicts favorable disease-free survival in patients with breast cancer

• Published in: Biochemical and biophysical research communications Vol. 458; no. 4; pp. 816 - 822
• Main Authors: Wang, Lei, Yao, Ling, Zheng, Yi-Zi, Xu, Qing, Liu, Xiu-Ping, Hu, Xin, Wang, Peng, Shao, Zhi-Ming
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.03.2015
• Subjects: Adult; Aged; Aged, 80 and over; ATG5; Autophagy; Autophagy-Related Protein 5; Breast - pathology; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - pathology; Cohort Studies; Disease-Free Survival; Female; FIP200; Humans; Immunohistochemistry; Microtubule-Associated Proteins - analysis; Middle Aged; Prognosis; Protein-Tyrosine Kinases - analysis; Retrospective Studies; FIP200; Breast cancer; Autophagy; Disease-free survival; ATG5
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.02.037

Autophagy is a self-digesting process that is primarily responsible for the removal and recycling of long-lived proteins and damaged organelles to maintain the homeostasis of the cell. Recent studies have indicated dual roles for autophagy in cancer: suppression of tumor progression and promotion of survival. In this study, we sought to investigate the prognostic value of two autophagy-related proteins, autophagy-related gene 5 (ATG5) and FAK family kinase-interacting protein of 200 kDa (FIP200), in patients with operable breast cancer. More specifically, the expression of ATG5 and FIP200 was evaluated by immunohistochemistry (IHC) in surgical specimens collected from 200 patients who were diagnosed with histologically proven invasive ductal breast cancer. A stepwise Cox multivariate analysis was then performed to construct a risk prediction model. In this retrospective cohort study, both ATG5 (HR = 0.465, 95% CI 0.247–0.872, P = 0.017) and FIP200 (HR = 0.521, 95% CI 0.278–0.979, P = 0.043) correlated with prolonged disease-free survival (DFS). In a receiver operating characteristic (ROC) analysis, the addition of ATG5 and FIP200 expression led to a significantly improved area under the time-dependent ROC curve (AUC) at 3 years (0.748 versus 0.680, P < 0.001) and 5 years (0.756 versus 0.699, P < 0.001). Collectively, our findings established the prognostic significance of ATG5 and FIP200 in patients with breast cancer. •High expression of autophagy-related proteins ATG5 and FIP200 correlates with prolonged disease-free survival in breast cancer.•We propose a risk prediction model using clinical variables (traditional model).•The addition of ATG5 and FIP200 expression (combined model) significantly improves the accuracy of risk prediction.•The combined model retains its good discriminatory power in subjects stratified by breast cancer subtype.