The ncRNA-Mediated Overexpression of Ferroptosis-Related Gene EMC2 Correlates With Poor Prognosis and Tumor Immune Infiltration in Breast Cancer

Abstract

Ferroptosis is an iron-dependent programmed cell death process. Although ferroptosis inducers hold promising potential in the treatment of breast cancer, the specific role and mechanism of the ferroptosis-related gene EMC2 in breast cancer have not been entirely determined. The potential roles of EMC2 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor Immune Estimation Resource (TIMER), Shiny Methylation Analysis Resource Tool (SMART), starBase, and cBioPortal for cancer genomics (cBioPortal) datasets. The expression difference, mutation, survival, pathological stage, DNA methylation, non-coding RNAs (ncRNAs), and immune cell infiltration related to EMC2 were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the differences in biological processes and functions among different related genes. The expression levels of core prognostic genes were then verified in breast invasive carcinoma samples using immunohistochemistry and breast invasive carcinoma cell lines using real-time polymerase chain reaction. High expression levels of EMC2 were observed in most cancer types. EMC2 expression in breast cancer tissue samples correlated with poor overall survival. EMC2 was mutated and methylated in a variety of tumors and affected survival. The LINC00665-miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of EMC2 in breast cancer. EMC2 levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Our study offers a comprehensive understanding of the oncogenic roles of EMC2 across different tumors. The upregulation of EMC2 expression mediated by ncRNAs is related to poor prognosis and tumor immune infiltration in breast cancer.

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

“…We found that proteins associated with longer PFS were most highly correlated with ES-TIL tumors, followed by S-TIL, and less so in those classified as N-TIL. We identified fifteen proteins that strongly correlated with PFS in our cohort, independent of common covariates of disease progression (e.g., patient age at diagnosis, disease stage and residual disease status), that included several proteins known to regulate antigen presentation 36 (TAP2, adjusted hazard ratio, aHR = 0.76, p = 0.02), T-cell activation 37 (SPN, aHR = 0.7, p = 0.014) and have further been correlated with regulating immune cell infiltration in other organ-site malignancies 38 (EMC2, aHR = 0.27, p = 4.4E−4). We investigated these immune-related candidates in transcript data from an independent cohort of 126 HGSOC patients 15 , many of whom survived greater than 10 years, and confirmed that these 15 immune-related proteins strongly correlate with PFS and OS.…”

ncRNAs-mediated high express of LPCAT1 correlates with poor prognosis and expression of tumor-related signaling pathway and tumor-related gene in breast cancer

“…starBase (ENCORI: The Encyclopedia of RNA Interactomes. (sysu.edu.cn)) is a database for exploring miRNA-related studies [30,31]. We use starBase to perform the expression correlation analysis for miRNA-LPCAT1, lncRNA-has-miR-218-5p and lncRNA-LPCAT1 in BRCA.…”

Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms

“…Cancer treatment has rapidly evolved into immunotherapy, and the effective therapy of established tumors necessitates rational multi-combination immunotherapy including ferroptosis. Recently, many studies have reported the interaction between ferroptosis modifications and antitumor immunity [4][5][6][7][8][9][10][11][12] . Ferroptosis, characterized by iron-dependent accumulation of lipid peroxides 13 ,…”