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.

Highlights

  • Cancer is the leading cause of death and an essential obstacle to increasing life expectancy, globally

  • We used Gene Expression Profiling Interactive Analysis 2 (GEPIA2) to analyze the influence of EMC2 expression on tumor grading and found significant differences in colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), kidney renal clear cell carcinoma (KIRC), and TCGT (Figure 1C)

  • The above results show that EMC2 is a potential oncogene for eight cancers

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Summary

Introduction

Cancer is the leading cause of death and an essential obstacle to increasing life expectancy, globally. According to the 2020 Global Cancer Statistics Report [1], female breast cancer had surpassed lung cancer to become the world’s most commonly diagnosed cancer, with an estimated 2.3 million new cases in 2020 (11.7%); it was the fifth leading cause of cancer deaths worldwide, with 685,000 deaths. Ferroptosis is considerably different from other cell death types in terms of morphology, molecular biology, and metabolic characteristics. The EMC is closely related to neurological diseases and tumors. Rare EMC1 mutations are associated with severe human neurodegenerative diseases, which manifest as growth retardation, cerebellar atrophy, scoliosis, hypotonia, psychomotor retardation, epilepsy, and craniofacial abnormalities [3,4,5]

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