期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 24, 期 16, 页码 9145-9153出版社
WILEY
DOI: 10.1111/jcmm.15551
关键词
autophagy; breast cancer; gene; model; prognosis
资金
- Medical Scientific Research Foundation of Guangdong Province [B2019039]
- National Natural Science Foundation of Guangdong Province [2016A030313768, 2018A030313292]
- National Natural Science Foundation of China [81902828, 81602645, 81071851, 81001189]
- Research Funds from Guangzhou Municipal Science and Technology Project [201707010418, 201804010430]
Accumulating evidence revealed that autophagy played vital roles in breast cancer (BC) progression. Thus, the aim of this study was to investigate the prognostic value of autophagy-related genes (ARGs) and develop a ARG-based model to evaluate 5-year overall survival (OS) in BC patients. We acquired ARG expression profiling in a large BC cohort (N = 1007) from The Cancer Genome Atlas (TCGA) database. The correlation between ARGs and OS was confirmed by the LASSO and Cox regression analyses. A predictive model was established based on independent prognostic variables. Thus, time-dependent receiver operating curve (ROC), calibration plot, decision curve and subgroup analysis were conducted to determine the predictive performance of ARG-based model. Four ARGs (ATG4A, IFNG, NRG1 and SERPINA1) were identified using the LASSO and multivariate Cox regression analyses. A ARG-based model was constructed based on the four ARGs and two clinicopathological risk factors (age and TNM stage), dividing patients into high-risk and low-risk groups. The 5-year OS of patients in the low-risk group was higher than that in the high-risk group (P < 0.0001). Time-dependent ROC at 5 years indicated that the four ARG-based tool had better prognostic accuracy than TNM stage in the training cohort (AUC: 0.731 vs 0.640,P < 0.01) and validation cohort (AUC: 0.804 vs 0.671,P < 0.01). The mutation frequencies of the four ARGs (ATG4A, IFNG, NRG1 and SERPINA1) were 0.9%, 2.8%, 8% and 1.3%, respectively. We built and verified a novel four ARG-based nomogram, a credible approach to predict 5-year OS in BC, which can assist oncologists in determining effective therapeutic strategies.
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