PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

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Abstract

Objective: We aim to identify the crucial genes or potential biomarkers associated with uterine fibroids (UFs), which may provide clinicians with evidence about the diagnostic biomarker of UFs and reveal the mechanism of its progression.

Methods: The gene expression and genome-wide DNA methylation profiles were obtained from Gene Expression Omnibus database (GEO). GSE45189, GSE31699, and GSE593 datasets were included. GEO2R and Venn diagrams were used to analyze the differentially expressed genes (DEGs) and extract the hub genes. Gene Ontology (GO) analysis was performed by the online tool Database for Annotation, Visualization, and Integrated Discovery (DAVID). The mRNA and protein expression of hub genes were validated by RT-qPCR, western blot, and immunohistochemistry. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value.

Results: We detected 22 DEGs between UFs and normal myometrium, which were enriched in cell maturation, apoptotic process, hypoxia, protein binding, and cytoplasm for cell composition. By finding the intersection of the data between differentially expressed mRNA and DNA methylation profiles, 3 hub genes were identified, including transmembrane 4 L six family member 1 (TM4SF1), TNF superfamily member 10 (TNFSF10), and proteolipid protein 1 (PLP1). PLP1 was validated to be up-regulated significantly in UFs both at mRNA and protein levels. The area under the ROC curve (AUC) of PLP1 was 0.956, with a sensitivity of 79.2% and a specificity of 100%. Conclusion: Overall, our results indicate that PLP1 may be a potential diagnostic biomarker for uterine fibroids.

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Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Kenneth Livak, Thomas D. Schmittgen (2001)

The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).

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Functions of DNA methylation: islands, start sites, gene bodies and beyond.

Peter A. Jones (2012)

DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.

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The DNA methyltransferases of mammals.

T Bestor (2000)

The biological significance of 5-methylcytosine was in doubt for many years, but is no longer. Through targeted mutagenesis in mice it has been learnt that every protein shown by biochemical tests to be involved in the establishment, maintenance or interpretation of genomic methylation patterns is encoded by an essential gene. A human genetic disorder (ICF syndrome) has recently been shown to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene. A second human disorder (Rett syndrome) has been found to result from mutations in the MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome stabilization. The majority of genomic 5-methylcytosine is now known to enforce the transcriptional silence of the enormous burden of transposons and retroviruses that have accumulated in the mammalian genome. It has also become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed. Although a number of outstanding questions have yet to be answered (one of these questions involves the nature of the cues that designate sites for methylation at particular stages of gametogenesis and early development), studies of DNA methyltransferases are likely to provide further insights into the biological functions of genomic methylation patterns.

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Lei Cai: URI : https://loop.frontiersin.org/people/1640654/overview

Zhiqi Liao: URI : https://loop.frontiersin.org/people/1191237/overview

Shiyu Li: URI : https://loop.frontiersin.org/people/1468079/overview

Jie Li: URI : https://loop.frontiersin.org/people/1535884/overview

Hanwang Zhang: URI : https://loop.frontiersin.org/people/1041797/overview

Journal

Journal ID (nlm-ta): Front Genet

Journal ID (iso-abbrev): Front Genet

Journal ID (publisher-id): Front. Genet.

Title: Frontiers in Genetics

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-8021

Publication date (Electronic): 31 October 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 1045395

Affiliations

[1] ¹ Reproductive Medicine Center , Tongji Hospital , Tongji Medical College , Huazhong University of Science and Technology , Wuhan, China

[2] ² Institute of Digestive Disease and Department of Medicine and Therapeutics , State Key Laboratory of Digestive Diseases , Li Ka Shing Institute of Health Sciences , The Chinese University of Hong Kong , Hong Kong, China

[3] ³ Department of Gynecology , First Affiliated Hospital of Zhengzhou University , Zhengzhou, China

Author notes

Edited by: Kunqi Chen, Fujian Medical University, China

Reviewed by: Qing Long, Kunming Medical University, China

Haolong Li, Peking Union Medical College Hospital, China

Ahmed Hammad, Egyptian Atomic Energy Authority, Egypt

Malihe Rastegarpanah, Breast Cancer Research Center, Motamed Cancer Institute, Iran

Haoran Shi, University of Giessen, Germany

*Correspondence: Hanwang Zhang, hwzhang605@ 123456126.com ; Fang Ren, fccrenf@ 123456zzu.edu.cn

This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Genetics

Article

Publisher ID: 1045395

DOI: 10.3389/fgene.2022.1045395

PMC ID: 9662689

PubMed ID: 36386836

SO-VID: 6b5e6a3a-b529-434e-918a-a080eccd5fa1

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

PLP1 may serve as a potential diagnostic biomarker of uterine fibroids

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G3: Genes|Genomes|Genetics

Most cited references 57

Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Functions of DNA methylation: islands, start sites, gene bodies and beyond.

The DNA methyltransferases of mammals.

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