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 poor prognosis. Therefore, it is imperative to develop new prognostic or therapeutic biomarkers for TNBC. Objective: 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 stage (P<0.05). Patent review suggested that many mTOR inhibitors alone or in combination with another anticancer agent have been provided for 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.

Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review

“…Prognostic indicators such as tumor size and lymph node metastases are insufficient for personalized treatment of patients with early-stage breast cancer. 82 Therefore, it is essential to identify molecular biomarkers and verify their usefulness as targets in personalized treatments and as indicators of clinical efficacy although achieving this is difficult owing to the lack of therapeutic targets. 83 , 84 Nevertheless, the following targets hold promise for patients with TNBC: PARP, insulin-like growth factor binding protein, PD-L1, interleukin-8, and glucocorticoid receptors.…”

The clinicopathological and prognostic significance of mTOR and p-mTOR expression in patients with non-small cell lung cancer: A meta-analysis

“…[32] Meanwhile, studies on the relationship between mTOR/p-mTOR expression and gastric cancer, breast cancer, colorectal cancer, nasopharyngeal carcinoma, and urinary system tumors have shown that mTOR or p-mTOR may be considered promising markers for predicting aggressiveness and prognosis of cancer. [33][34][35][36][37] In NSCLC, dysregulation of Akt/ mTOR signaling pathway activity is one of the primary factors of carcinogenesis. mTOR promotes tumorigenesis and progression through activation of the downstream eIF4 complexes.…”