Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer

Abstract

Background: Breast cancer is the mostly diagnosed cancer worldwide, and triple negative breast cancer (TNBC) has the worst prognosis. Cuproptosis is a newly identified form of cell death, whose mechanism has not been fully explored in TNBC. This study thought to unveil the potential association between cuproptosis and TNBC.Materials and Methods: Gene expression files with clinical data of TNBC downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were included in this study. Consensus clustering was utilized to perform molecular subtyping based on cuproptosis-associated genes. Limma package was applied to distinguish differentially expressed genes. Univariate Cox regression was used to identify prognostic genes. Least absolute shrinkage and selection operator and stepwise Akaike information criterion optimized and established a risk model.Results: We constructed three molecular subtypes based on cuproptosis-associated genes, and the cuproptosis-based subtyping showed a robustness in different datasets. Clust2 showed the worst prognosis and immune-related pathways such as chemokine signaling pathway were significantly activated in clust2. Clust2 also exhibited a high possibility of immune escape to immune checkpoint blockade. In addition, a six-gene risk model was established manifesting a high AUC score over 0.85 in TCGA dataset. High- and low-risk groups had distinct prognosis and immune infiltration. Finally, a nomogram was constructed with strong performance in predicting TNBC prognosis than the staging system.Conclusion: The molecular subtyping system related to cuproptosis had a potential in guiding immunotherapy for TNBC patients. Importantly, the six-gene risk model was effective and reliable to predict TNBC prognosis.

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

“…CRGs influence the clinicopathologic characteristics, prognosis, and tumor microenvironment and show a significant association with tumor immunity in TNBC [ 9 ]. A six-gene risk model demonstrated effective prognostic prediction for patients with TNBC [ 10 ]. Nonetheless, the biological functions and prognostic significance of cuproptosis-related miRNAs and the target genes regulated by them have not been reported.…”

“…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.…”

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

“…All of the above information resulted in the present manuscript and the decision to further investigate the SAC effect on proliferation and expression of the MPST, CTH, and CBS enzymes with broadened cancer model. The choice of two adenocarcinoma cell lines was made in accordance with our extended previous research regarding the MCF-7 cell line [25] and with the careful consideration of the literature regarding the MDA-MD-231 as a representant of the triple-negative breast cancer, characterized as the most malignant and the most difficult to treat [41,42], as well as one being potent to SAC exposure. In research from 2008, Gapter et al [43] presented the results regarding sub-lethal SAC-treatment as one altering mammary tumor cell adhesion and invasion through components of the extracellular matrix in MDA-MB-231 cells.…”

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

“…Among the limited bioinformatics studies in BC, it is true that estimating cuproptosis patterns in tumors could help predict the prognosis and characteristics of TME cell infiltration and guide more effective chemotherapeutic and immunotherapeutic strategies [ 7 ]. However, current BC studies based on publicly available data only use the overall BC cases, and in particular, there are very limited research of cuproptosis involvement in the prognosis of TNBC by bioinformatic analysis [ 14 , 15 ]. Given that TNBC is the most malignant subtype of BC, it is particularly significant to explore the potential mechanisms of progression and treatment strategies.…”