Insights into prognosis and immune infiltration of cuproptosis-related genes in breast cancer

Abstract

IntroductionBreast cancer (BC) has been ranking first in incidence and the leading cause of death among female cancers worldwide based on the latest report. Regulated cell death (RCD) plays a significant role in tumor initiation and provides an important target of cancer treatment. Cuproptosis, a novel form of RCD, is ignited by mitochondrial stress, particularly the lipoylated mitochondrial enzymes aggregation. However, the role of cuproptosis-related genes (CRGs) in tumor generation and progression remains unclear.MethodsIn this study, the mRNA expression data of CRGs in BC and normal breast tissue were extracted from TCGA database, and protein expression patterns of these CRGs were analyzed using UALCAN. The prognostic values of CRGs in BC were explored by using KaplanMeier plotter and Cox regression analysis. Genetic mutations profiles were evaluated using the cBioPortal database. Meanwhile, we utilized CIBERSORT and TIMER 2.0 database to perform the correlation analysis between CRGs and immune cell infiltration.ResultsOur results indicated that CRGs expression is significantly different in BC and normal breast tissues. Then we found that upregulated PDHA1 expression was associated with worse endpoint of BC. Moreover, we also performed immune infiltration analysis of CRGs, and demonstrated that PDHA1 expression was closely related to the infiltration levels of CD4+ memory T cell, macrophage M0 and M1 cell and mast cell in BC.ConclusionsOur results demonstrated the prognostic and immunogenetic values of PDHA1 in BC. Therefore, PDHA1 can be an independent prognostic biomarker and potential target for immunotherapy of BC.

Identification and validation of a novel risk model based on cuproptosis‑associated m6A for head and neck squamous cell carcinoma

“…Conversely, overexpression of METTL3 can elevate m6A levels in glioblastoma stem cells and suppress their growth. Moreover, studies have shown that CDKN2A sensitizes the cells to cuproptosis [ 10 , 29 ]. Our investigation has recognized CDKN2A as a safeguarding gene in determining the prognosis of HNSCC patients.…”

Identification and validation of a copper homeostasis-related gene signature for the predicting prognosis of breast cancer patients via integrated bioinformatics analysis

“…Similarly, a separate study presented a cuproptosis-related gene signature (involving TNFRSF18, SLC1A1, among others) to assess patient outcomes and the tumor immune environment, although it lacked clinical sample validation 25 . Pan et al identified and validated 10 cuproptosis-related lncRNAs in 12 BC patients and cell lines 26 , while Huang et al concentrated on cuproptosis-related genes, identifying PDHA1 as an independent BC prognostic biomarker, validated in cell lines and a 30-sample tissue microarray 27 . However, current research focusing on lncRNAs related to copper homeostasis, instead of those associated with cuproptosis and breast cancer, is still largely uncharted.…”

Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration

“…GeneMANIA is an online resource which can explore gene functionality, analyze gene cluster, and prioritize genes for functional assay 14 . In our study, GeneMANIA website was utilized to dissect and categorize the interaction between PDK genes and their related genes.…”