Identification and Verification of Diagnostic Biomarkers for Deep Infiltrating Endometriosis Based on Machine Learning Algorithms

Overview

Journal J Biol Eng

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2024 Nov 26

PMID 39587559

Authors

Shanping Shi

Chao Huang

Xiaojian Tang

Hua Liu

Weiwei Feng

Chen Chen

Affiliations

Soon will be listed here.

Abstract

This study addresses the challenges in the early diagnosis of deep infiltrating endometriosis (DIE) by exploring the potential role of the deubiquitinating enzyme USP14. By analyzing the GSE141549 dataset from the Gene Expression Omnibus (GEO) database, using bioinformatics methods and three machine learning algorithms (LASSO, Random Forest, and Support Vector Machine), the key feature gene USP14 was identified. The results indicated that USP14 is significantly upregulated in DIE and exhibits good predictive value (AUC = 0.786). Further analysis revealed the important role of USP14 in muscle function, cellular growth factor response, and maintenance of chromosome structure, and its close association with various immune cell functions. Immunohistochemical staining confirmed the high expression of USP14 in DIE tissues. This study provides a new molecular target for the early diagnosis of DIE, which holds significant clinical implications and potential application value.

References

Brichant G, Laraki I, Henry L, Munaut C, Nisolle M . New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments. Int J Mol Sci. 2021; 22(19). PMC: 8508913. DOI: 10.3390/ijms221910498. View

DAndrea A, Pellman D . Deubiquitinating enzymes: a new class of biological regulators. Crit Rev Biochem Mol Biol. 1998; 33(5):337-52. DOI: 10.1080/10409239891204251. View

Pereira W, Almeida F, Conde D, Balmant K, Triozzi P, Schmidt H . Asc-Seurat: analytical single-cell Seurat-based web application. BMC Bioinformatics. 2021; 22(1):556. PMC: 8600690. DOI: 10.1186/s12859-021-04472-2. View

Wang Y, Wang J, Zhong J, Deng Y, Xi Q, He S . Ubiquitin-specific protease 14 (USP14) regulates cellular proliferation and apoptosis in epithelial ovarian cancer. Med Oncol. 2014; 32(1):379. DOI: 10.1007/s12032-014-0379-8. View

Chen B, Khodadoust M, Liu C, Newman A, Alizadeh A . Profiling Tumor Infiltrating Immune Cells with CIBERSORT. Methods Mol Biol. 2018; 1711:243-259. PMC: 5895181. DOI: 10.1007/978-1-4939-7493-1_12. View

Baranov V, Ivaschenko T, Liehr T, Yarmolinskaya M . Systems genetics view of endometriosis: a common complex disorder. Eur J Obstet Gynecol Reprod Biol. 2014; 185:59-65. DOI: 10.1016/j.ejogrb.2014.11.036. View

Falcone T, Flyckt R . Clinical Management of Endometriosis. Obstet Gynecol. 2018; 131(3):557-571. DOI: 10.1097/AOG.0000000000002469. View

Koninckx P, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin D . Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril. 2018; 111(2):327-340. DOI: 10.1016/j.fertnstert.2018.10.013. View

Wang F, Ning S, Yu B, Wang Y . USP14: Structure, Function, and Target Inhibition. Front Pharmacol. 2022; 12:801328. PMC: 8766727. DOI: 10.3389/fphar.2021.801328. View

10.

Ferreira M, Santos G, Biagi C, Silva Junior W, Zambuzzi W . GSVA score reveals molecular signatures from transcriptomes for biomaterials comparison. J Biomed Mater Res A. 2020; 109(6):1004-1014. DOI: 10.1002/jbm.a.37090. View

11.

Li Q, Yuan M, Jiao X, Huang Y, Li J, Li D . M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis. Front Immunol. 2021; 12:707784. PMC: 8329654. DOI: 10.3389/fimmu.2021.707784. View

12.

Wang Y, Nicholes K, Shih I . The Origin and Pathogenesis of Endometriosis. Annu Rev Pathol. 2019; 15:71-95. PMC: 7980953. DOI: 10.1146/annurev-pathmechdis-012419-032654. View

13.

Koninckx P, Martin D . Deep endometriosis: a consequence of infiltration or retraction or possibly adenomyosis externa?. Fertil Steril. 1992; 58(5):924-8. DOI: 10.1016/s0015-0282(16)55436-3. View

14.

Koninckx P, Ussia A, Adamyan L, Wattiez A, Donnez J . Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012; 98(3):564-71. DOI: 10.1016/j.fertnstert.2012.07.1061. View

15.

Gong X, Jia L, Zhou L, Hu T . USP14 predicts poorer survival outcomes and promotes tumor progression in endometrial carcinoma by activating NF-κB signaling. Aging (Albany NY). 2023; 15(21):12120-12135. PMC: 10683613. DOI: 10.18632/aging.205168. View

16.

Harrigan J, Jacq X, Martin N, Jackson S . Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov. 2017; 17(1):57-78. PMC: 7097658. DOI: 10.1038/nrd.2017.152. View

17.

Gonzalez-Marquez R, Schmidt L, Schmidt B, Berens P, Kobak D . The landscape of biomedical research. Patterns (N Y). 2024; 5(6):100968. PMC: 11240179. DOI: 10.1016/j.patter.2024.100968. View

18.

Gueuvoghlanian-Silva B, Bellelis P, Barbeiro D, Hernandes C, Podgaec S . Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease. J Reprod Immunol. 2018; 126:32-38. DOI: 10.1016/j.jri.2018.02.003. View

19.

Piketty M, Chopin N, Dousset B, Millischer-Bellaische A, Roseau G, Leconte M . Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination. Hum Reprod. 2008; 24(3):602-7. DOI: 10.1093/humrep/den405. View

20.

Mines M, Goodwin J, Limbird L, Cui F, Fan G . Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation. J Biol Chem. 2008; 284(9):5742-52. PMC: 2645827. DOI: 10.1074/jbc.M808507200. View