Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients - TCGA Data Analysis

Sep 21, 2026

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ERβ has been assigned a tumor suppressor role, yet tissue-specific expression and function remain unclear due to conflicting reports. A gap persists in integrated analyses of ESR2 mRNA expression across tumor types and in mapping its potential gene network. Using comprehensive TCGA transcriptomic data, cancer types with significant ESR2 expression changes versus healthy tissue were identified, and ESR2 was linked to patient survival. Gene Set Enrichment Analysis highlighted ESR2-associated pathways, including oxidative phosphorylation and epithelial–mesenchymal transition. Co-expression analysis revealed ESR2-patterned genes potentially affecting clinical outcomes, including ACIN1, SYNE2, TNFRSF13C, and MDM4, defining ESR2’s impact on tumor transcriptomic organization and metabolism.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages34

Reading Time1 h 26 min

AccessFree to download

Introduction

ESR2/ERβ background and receptor biology

Genomic and non-genomic ERβ signaling

Methods and Results

ESR2 expression differences across cancer and healthy tissues

ESR2 association with patient survival

GSEA: pathways related to ESR2

ESR2 co-expressed gene identification

Article Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis Julia Maria Lipowicz 1, Agnieszka Mali ´nska 2, Michał Nowicki 2 and Agnieszka Anna Rawłuszko-Wieczorek 2, * Citation: Lipowicz, J.M.; Mali ´nska, A.; Nowicki, M.; Rawłuszko-Wieczorek, A.A. Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis. Int. J. Mol. Sci. 2024, 25, 8707. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25168707](doi.org/10.3390/ijms25168707) Academic Editor: Erik A.C. Wiemer Received: 26 June 2024 Revised: 2 August 2024 Accepted: 7 August 2024 Published: 9 August 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Histology and Embryology, Doctoral School, Poznan University of Medical Sciences,´Swi˛ecickiego 6 Street, 60-781 Pozna ´n, Poland; [julia.lipowicz@student.ump.edu.pl](julia.lipowicz@student.ump.edu.pl) 2 Department of Histology and Embryology, Poznan University of Medical Sciences, ´Swi˛ecickiego 6 Street, 60-781 Pozna ´n, Poland * Correspondence: [arawluszko@ump.edu.pl](arawluszko@ump.edu.pl) Abstract: ERβ has been assigned a tumor suppressor role in many cancer types. However, as conflicting findings emerge, ERβ’s tissue-specific expression and functional role have remained elusive. There remains a notable gap in compact and comprehensive analyses of ESR2 mRNA expression levels across diverse tumor types coupled with an exploration of its potential gene network. In this study, we aim to address these gaps by presenting a comprehensive analysis of ESR2 transcriptomic data. We distinguished cancer types with significant changes in ESR2 expression levels compared to corresponding healthy tissue and concluded that ESR2 influences patient survival. Gene Set Enrichment Analysis (GSEA) distinguished molecular pathways affected by ESR2, including oxidative phosphorylation and epithelial–mesenchymal transition. Finally, we investigated genes displaying similar expression patterns as ESR2 in tumor tissues, identifying potential co-expressed genes that may exert a synergistic effect on clinical outcomes, with significant results, includingthe expression of ACIN1, SYNE2, TNFRSF13C, and MDM4 . Collectively, our results highlight the significant influence of ESR2 mRNA expression on the transcriptomic landscape and the overall metabolism of cancerous cells across various tumor types. Keywords: cancer; ESR2; bioinformatic; gene expression; transcriptomic; survival 1. Introduction Estrogen receptor β (ERβ) is one of the three predominant 17β-estradiol (E2) receptors in cells, along with estrogen receptor α (ERα) and G-protein-coupled estrogen receptor 1 (GPER1) [1] . ERβ and ERα are members of the nuclear receptor superfamily, while GPER1 is present on cell membranes [2,3] . ERβ is encoded by the gene ESR2, located on chromosome 14, containing eight exons. As ESR2 is susceptible to alternative splicing, it can be transcribed into six isoforms, with ERβ1 characterized as the wild-type, fulllength (530-amino-acids long, 59 kDa) protein [3–5] . For a full review and comparison of different ERs and their structure, we recommend perusing studies by Božovi´c et al. [3] and Jia et al. [1] . ERβ displays diverse functions through genomic (nuclear, otherwise called classical) and non-genomic (rapid, extranuclear) pathways [6] . The classical pathways are initiated by the ligand-bound ERβ-E2 complex. This complex translocates into the nucleus, where it orchestrates the transcriptional regulation of target genes. The recognition of target genes can be mediated through the estrogen response element (ERE) canonical

FAQs

What is ESR2 and how is it related to ERβ in cancer biology?

ESR2 encodes estrogen receptor β (ERβ). The study background describes ERβ as one of the main estrogen receptors and discusses its genomic and non-genomic signaling roles.

How did the analysis evaluate ESR2 expression across cancer types?

The study compared ESR2 transcriptomic data between tumor tissues and corresponding healthy tissue to find cancer types with significant ESR2 expression changes.

What did ESR2 expression reveal about clinical outcomes for patients?

The results concluded that ESR2 influences patient survival, and further analyses connected ESR2 to molecular pathways and co-expressed genes relevant to clinical outcomes.

Sep 21, 2026

Uploaded by Asher