The therapeutic and prognostic role of cuproptosis-related genes in triple negative breast cancer

Abstract

Background This study aimed to observe the potential impact of known cuproptosis-related genes (CRGs) on triple negative breast cancer (TNBC) development, as well as their associated molecular mechanisms, immune infiltration mechanisms and potential therapeutic agents. Results Based on the Cox Proportional Hazard Model, 11 CRGs may be especially important in TNBC development and progression (considered as the Key-TNBC-CRGs). The expression of several Key-TNBC-CRGs (e.g., ATP7A, PIK3CA, LIAS, and LIPT) are associated with common mutations. The SCNA variation of 11 Key-TNBC-CRGs are related to differences immune infiltration profiles. In particular, depletion of ATP7A, ATP7B, CLS, LIAS, and SCL31A1 and while high amplification of NLRP3 and LIPT2 are correlated with decreased immune infiltration. In our Cox proportional hazards regression model, there is a significant difference in the overall survival between high-risk and low-risk groups. The HR in the high-risk group is 3.891 versus the low-risk group. And this model has a satisfactory performance in Prediction of 5–15-year survival, in particular in the 10-year survival (AUC = 0.836). Finally, we discovered some potential drugs for TNBC treatment based on the strategy of targeting 11 Key-TNBC-CRGs, such as Dasatinib combined with ABT-737, Erastin or Methotrexate, and Docetaxel/Ispinesib combination. Conclusion In conclusion, CRGs may play important roles in TNBC development, and they can impact tumor immune microenvironment and patient survival. The Key-TNBC-CRGs interact mutually and can be influenced by common BC-related mutations. Additionally, we established a 11-gene risk model with a robust performance in prediction of 5–15-year survival. As well, some new drugs are proposed potentially effective in TNBC based on the CRG strategy.

Micronutrient Status and Breast Cancer: A Narrative Review

“…The effective rate of the experimental group with the treatment of radioactive seed 125 I implantation under CT guidance was statistically higher than in the control group with conventional therapy.…”

“…It is involved in the cellular metabolism as a catalytic cofactor in the regulation of energy production, oxygen transport, iron storage, signal transduction, and other intracellular processes. Even a small increase in Cu concentration in the body can cause severe toxicity, oxidative stress, initiation, and promotion of carcinogenesis [124,125]. The 2022 case-control study by Barartabar et al showed that the Cu levels (p = 0.0001) in tumor tissue were significantly higher than in tumor margin tissue in 40 women with a histologically confirmed diagnosis of invasive ductal carcinoma [122].…”

“…It was also shown that PDHA1 overexpression was significantly associated with a negative prognosis in patients with breast cancer due to low overall survival (OS) and low recurrence-free survival (RFS) rates [124]. Shi et al (2023), using bioinformatics analysis, identified 11 CRGs associated with the development of TNBC: NFE2L2, NLRP3, ATP7B, ATP7A, SLC31A1, LIAS, LIPT1, DLAT, PDHB, GLS, and DLST [116]. Based on these, an 11-gene risk model effective in predicting 5-, 10-, and 15-year survival in patients with TNBC was also developed [125].…”

“…Shi et al (2023), using bioinformatics analysis, identified 11 CRGs associated with the development of TNBC: NFE2L2, NLRP3, ATP7B, ATP7A, SLC31A1, LIAS, LIPT1, DLAT, PDHB, GLS, and DLST [116]. Based on these, an 11-gene risk model effective in predicting 5-, 10-, and 15-year survival in patients with TNBC was also developed [125].…”

Identification of cuproptosis-related miRNAs in triple-negative breast cancer and analysis of the miRNA–mRNA regulatory network

“…CRGs exhibit a close association with tumor immunity in TNBC and can serve as predictive markers for patient prognosis [ 9 ]. Current research endeavors have concentrated on exploring the potential prognostic significance of CRGs in TNBC, demonstrating a close correlation between CRGs and tumor immunity in TNBC [ [9] , [10] , [11] ]. However, miRNAs associated with TNBC have not been explored to date.…”