The Role of ATG4A Clinical Implication and Potential Function in Breast Cancer

Abstract

We studied the clinical implication and potential function of ATG4A in breast cancer by using publicly accessible patient data. The mRNA and protein levels of ATG4A were up-regulated in breast cancer tissues compared with normal breast tissues. ATG4A is a potential marker for prognosis, diagnosis and therapeutic target for breast cancer. Autophagy is a conservative catabolic process for cell homeostasis. The mechanism of autophagy in tumors is very complicated, since it can either promote or inhibit the occurrence and development of tumor according to different tumor stages and types. The purpose of this study was to investigate the clinical significance of an autophagy-related gene ATG4A in breast cancer. Transcriptional expression profiles of ATG4A between breast cancer tissues and normal tissues were retrieved from the Cancer Genome Atlas (TCGA). The ATG4A protein level was assessed by the Human Protein Atlas. The co-expression genes with ATG4A expression were analyzed using the LinkedOmics database. Protein–protein interaction (PPI) networks were constructed by the STRING. Paired t-test and Mann-Whitney U-test were used to determine the differences between breast cancer tissues and adjacent normal tissues. Kaplan–Meier curves and log rank tests were conducted for survival analysis. The expression of ATG4A in breast cancer tissues was significantly upregulated than those in adjacent normal tissues. Increased ATG4A mRNA expression was positively associated with lymph node metastases (P <0.05), ER positive (P <0.001), PR positive (P <0.001), HER-2 positive (P <0.05) and over 60 years of age (P <0.005). Compared with breast cancer patients with LumA, LumB and HER-2 positive subtypes, the expression of ATG4A mRNA in breast cancer patients with Basal was significantly lower (P <0.001). Kaplan–Meier survival analysis showed that the OS (P <0.001), DSS (P = 0.017) and PFI (P = 0.020) of breast cancer patients with high ATG4A mRNA expression were significantly shorter than those with low ATG4A mRNA expression. GO and KEGG analysis showed that Endocytosis might be a signal pathway involved in the occurrence and development of breast cancer by ATG4A. Furthermore, we found that RPL4, RPL11, RPL14, RPL29 and RPS9 may be the potential interacting genes of ATG4A in breast cancer by PPI analysis. ATG4A may be a potential diagnostic, prognostic biomarker and therapeutic target gene for breast cancer at the mRNA and protein levels.