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

Huang, Tingting; Liu, Yankuo; Li, Jiwei; Shi, Bingbing; Shan, Zhengda; Shi, Zhiyuan; Yang, Zhangru

doi:10.3389/fimmu.2022.1054305

Cited by 10 publications

(6 citation statements)

References 53 publications

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“…Tumor-in ltrating immune cells play an independent role in the TME, impacting the onset, course, and metastasis of cancer [15]. In patients with LUAD, our survival study showed a strong relationship between OS and RFS and the expression of ELOVL2, ELOVL6, and ELOVL7.…”

Section: Connection Between Elovls Expression and Immune Cell In Ltra...mentioning

confidence: 60%

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Li,

Zhang,

Jin

et al. 2024

Preprint

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Introduction: Lung adenocarcinoma (LUAD) has drawn attention recently because of its poor prognosis, limited responsiveness to treatment, and lack of trustworthy markers for predicting its development or its response to treatment. It has been established that the pathophysiology and development of various diseases, including malignancies, are influenced by the elongation of the very-long-chain fatty acids gene family (ELOVLs), a collection of genes responsible for elongating saturated and polyunsaturated fatty acids. Unknown is the specific function of ELOVLs in LUAD. Thus, the goal of our research was to elucidate the immune response and prognostic significance linked to ELOVL genes in LUAD. Methods: Open-access resources such as the TCGA and GTEx datasets were used to analyze the gene expression of ELOVLs across various types of cancers. We investigated the prognostic significance of the ELOVL family using Kaplan-Meier analysis. The cBioPortal database was utilized to assess the ELOVLs' genetic mutation profile. Several techniques were employed to get an understanding into the connection between tumor immunity and ELOVL genes. The WebGestalt database was used to carry out the function and pathway enrichment study of the ELOVL family. Immunohistochemical staining was utilized for the purpose of experimental validation. Results: We observed a substantial increase in gene expression in ELOVL1, ELOVL2, ELOVL4, ELOVL6, and ELOVL7 when comparing LUAD tumor samples to normal tissues. The upregulation of ELOVL2, ELOVL6, and ELOVL7 has been linked to tumor development and worse clinical outcome. The relevance was further highlighted by our examination of the immune infiltration pattern, which revealed a robust relationship between ELOVL2 expression and mast cell, macrophage, naive B cell, and myeloid dendritic cell in LUAD. ELOVL6 expression exhibited close association with B cell, macrophage, mast cell, CD4+ memory T cell, neutrophil, NK cell, and follicular helper T cell in LUAD. ELOVL7 expression exhibited close association with B cell, macrophage, mast cell, CD4+ memory T cell in LUAD. Conclusions: This study showed the significant immunogenetic and prognostic importance of ELOVL2, ELOVL6, and ELOVL7 in LUAD. Our findings highlight the importance of these genes and imply that they could function as distinct prognostic markers. Their discovery as immunotherapeutic targets offers an important benefit in fighting against LUAD.

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Section: Connection Between Elovls Expression and Immune Cell In Ltra...mentioning

confidence: 60%

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Li,

Zhang,

Jin

et al. 2024

Preprint

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Xing,

Xu,

et al. 2024

BMC Med Genomics

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Background Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a poor survival rate due to anatomical limitations of the head and a lack of reliable biomarkers. Cuproptosis represents a novel cellular regulated death pathway, and N6-methyladenosine (m6A) is the most common internal RNA modification in mRNA. They are intricately connected to tumor formation, progression, and prognosis. This study aimed to construct a risk model for HNSCC using a set of mRNAs associated with m6A regulators and cuproptosis genes (mcrmRNA). Methods RNA-seq and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to develop a risk model through the least absolute shrinkage and selection operator (LASSO) analysis. Survival analysis and receiver operating characteristic (ROC) analysis were performed for the high- and low-risk groups. Additionally, the model was validated using the GSE41613 dataset from the Gene Expression Omnibus (GEO) database. GSEA and CIBERSORT were applied to investigate the immune microenvironment of HNSCC. Results A risk model consisting of 32 mcrmRNA was developed using the LASSO analysis. The risk score of patients was confirmed to be an independent prognostic indicator by multivariate Cox analysis. The high-risk group exhibited a higher tumor mutation burden. Additionally, CIBERSORT analysis indicated varying levels of immune cell infiltration between the two groups. Significant disparities in drug sensitivity to common medications were also observed. Enrichment analysis further unveiled significant differences in metabolic pathways and RNA processing between the two groups. Conclusions Our risk model can predict outcomes for HNSCC patients and offers valuable insights for personalized therapeutic approaches.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Li,

Wei,

Wang

et al. 2024

Sci Rep

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The prognostic value of copper homeostasis-related genes in breast cancer (BC) remains largely unexplored. We analyzed copper homeostasis-related gene profiles within The Cancer Genome Atlas Program breast cancer cohorts and performed correlation analysis to explore the relationship between copper homeostasis-related mRNAs (chrmRNA) and lncRNAs. Based on these results, we developed a gene signature-based risk assessment model to predict BC patient outcomes using Cox regression analysis and a nomogram, which was further validated in a cohort of 72 BC patients. Using the gene set enrichment analysis, we identified 139 chrmRNAs and 16 core mRNAs via the Protein–Protein Interaction network. Additionally, our copper homeostasis-related lncRNAs (chrlncRNAs) (PINK1.AS, OIP5.AS1, HID.AS1, and MAPT.AS1) were evaluated as gene signatures of the predictive model. Kaplan–Meier survival analysis revealed that patients with a high-risk gene signature had significantly poorer clinical outcomes. Receiver operating characteristic curves showed that the prognostic value of the chrlncRNAs model reached 0.795 after ten years. Principal component analysis demonstrated the capability of the model to distinguish between low- and high-risk BC patients based on the gene signature. Using the pRRophetic package, we screened out 24 anticancer drugs that exhibited a significant relationship with the predictive model. Notably, we observed higher expression levels of the four chrlncRNAs in tumor tissues than in the adjacent normal tissues. The correlation between our model and the clinical characteristics of patients with BC highlights the potential of chrlncRNAs for predicting tumor progression. This novel gene signature not only predicts the prognosis of patients with BC but also suggests that targeting copper homeostasis may be a viable treatment strategy.

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

Cited by 10 publications

References 53 publications

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

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

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

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