Prognostic and Therapeutic Values of Autophagy-related Genes in Triple-negative Breast Cancer

Abstract

Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with a poor prognosis. Therefore, it is imperative to develop new prognostic or therapeutic biomarkers for TNBC.

Objectives: To explore the prognostic and therapeutic values of autophagy-related genes (ARGs) in TNBC.

Methods: Overall, 157 TNBC patients' data were obtained from The Cancer Genome Atlas database, and the ARGs were acquired from the Human Autophagy Database. Differentially expressed ARGs (DEGs) between tumor and normal tissues were identified, and the prognostic ARGs were developed using R software. Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves were both used to evaluate the accuracy of the signature. Patents about prognostic ARGs were reviewed through Worldwide Espacenet® and Patentscope®.

Results: We obtained 28 DEGs and two prognostic ARGs (EIF4EBP1 and PARP1). The Kaplan- Meier survival curves showed that the survival rate of patients with low 2-ARG signature risk score was significantly higher than that of patients with high-risk score (P =0.003). ROC at 5 years indicated that the signature had good prognostic accuracy (AUC =0.929). The signature was independent of T, N, M, and TNM stages (P <0.05). The patent review suggested that many mTOR inhibitors alone or in combination with another anticancer agent have been provided for the treatment of many cancers and shown promising results. No drug patents about PARP1 overexpression were disclosed.

Conclusion: We developed a 2-ARG signature (EIF4EBP1 and PARP1), which was an independent prognostic biomarker for TNBC. As EIF4EBP1 was upregulated in TNBC, mTOR inhibitors which blocked the mTOR/4EBP1/eIF4E pathway, may be a promising therapeutic strategy for TNBC.

Keywords: EIF4EBP1; PARP1; Triple-negative breast cancer; autophagy-related genes; mTOR inhibitor; prognostic signature.