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Li J, Xu S, Zhu F, Shen F, Zhang T, Wan X, Gong S, Liang G, Zhou Y. Multi-omics Combined with Machine Learning Facilitating the Diagnosis of Gastric Cancer. Curr Med Chem 2024; 31:6692-6712. [PMID: 38351697 DOI: 10.2174/0109298673284520240112055108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/28/2023] [Accepted: 01/03/2024] [Indexed: 10/19/2024]
Abstract
Gastric cancer (GC) is a highly intricate gastrointestinal malignancy. Early detection of gastric cancer forms the cornerstone of precision medicine. Several studies have been conducted to investigate early biomarkers of gastric cancer using genomics, transcriptomics, proteomics, and metabolomics, respectively. However, endogenous substances associated with various omics are concurrently altered during gastric cancer development. Furthermore, environmental exposures and family history can also induce modifications in endogenous substances. Therefore, in this study, we primarily investigated alterations in DNA mutation, DNA methylation, mRNA, lncRNA, miRNA, circRNA, and protein, as well as glucose, amino acid, nucleotide, and lipid metabolism levels in the context of GC development, employing genomics, transcriptomics, proteomics, and metabolomics. Additionally, we elucidate the impact of exposure factors, including HP, EBV, nitrosamines, smoking, alcohol consumption, and family history, on diagnostic biomarkers of gastric cancer. Lastly, we provide a summary of the application of machine learning in integrating multi-omics data. Thus, this review aims to elucidate: i) the biomarkers of gastric cancer related to genomics, transcriptomics, proteomics, and metabolomics; ii) the influence of environmental exposure and family history on multiomics data; iii) the integrated analysis of multi-omics data using machine learning techniques.
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Affiliation(s)
- Jie Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Siyi Xu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Feng Zhu
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
| | - Fei Shen
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
| | - Tianyi Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xin Wan
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Saisai Gong
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Geyu Liang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Yonglin Zhou
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
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Shareena G, Kumar D. Epigenetics of Epstein Barr virus - A review. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166838. [PMID: 37544529 DOI: 10.1016/j.bbadis.2023.166838] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 07/14/2023] [Accepted: 07/31/2023] [Indexed: 08/08/2023]
Abstract
Epstein Barr is the first-in-human oncogenic virus, closely related to numerous lymphoproliferative and malignant diseases, including HL, BL, NPC, and GC. EBV establishes life-long persistence infection portraying a biphasic viral life cycle: latent period and lytic replication. B-cells serve as critical regions for EBV latent genes, wherein viral gene expression is suppressed, promoting viral genome maintenance and immune recognition evasion. Upon its lytic reactivation, viral gene expression induces its replication, progeny production, and transmission. Dysregulations of epigenetic regulation in expressions of TSGs lead to carcinogenesis. Several studies reveal that EBV is associated with aberrant viral DNA and host genome methylation patterns, promoting immune monitoring, recognition evasiveness and host cell persistence. Among other epigenetic modifications, DNA methylation suppresses the majority of viral latent gene promoters, sparing a few, and acts as a prerequisite for activating EBV's lytic cycle, giving rise to viral progeny. It affects the host's epigenome via reprogramming cells to oncogenic, long-lasting phenotypes, as evident in several malignancies. At each phase of its life cycle, EBV exploits cellular mechanisms of epigenetic regulation, implying its unique host-pathogen relationship. This review summarized the DNA methylation's regulatory roles on several EBV-related promoter regions, along with the host genome in pathological conditions, highlights viral genes involved in a latent, lytic and latent-lytic phase of EBV infection. Moreover, it provides diagrammatic insights into methylation-based pathways in EBV.
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Affiliation(s)
- Gadde Shareena
- Poona College of Pharmacy, Department of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to be University), Erandwane, Pune 411038, Maharashtra, India
| | - Dileep Kumar
- Poona College of Pharmacy, Department of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to be University), Erandwane, Pune 411038, Maharashtra, India; UC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California Davis, One Shields Avenue, Davis, CA 95616, USA.
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The roles of DNA methylation on the promotor of the Epstein–Barr virus (EBV) gene and the genome in patients with EBV-associated diseases. Appl Microbiol Biotechnol 2022; 106:4413-4426. [PMID: 35763069 PMCID: PMC9259528 DOI: 10.1007/s00253-022-12029-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 06/11/2022] [Accepted: 06/13/2022] [Indexed: 11/22/2022]
Abstract
Abstract Epstein–Barr virus (EBV) is an oncogenic virus that is closely associated with several malignant and lymphoproliferative diseases. Studies have shown that the typical characteristic of EBV-associated diseases is aberrant methylation of viral DNA and the host genome. EBV gene methylation helps EBV escape from immune monitoring and persist in host cells. EBV controls viral gene promoter methylation by hijacking host epigenetic machinery to regulate the expression of viral genes. EBV proteins also interact with host epigenetic regulatory factors to mediate the methylation of the host’s important tumour suppressor gene promoters, thereby participating in the occurrence of tumorigenesis. Since epigenetic modifications, including DNA methylation, are reversible in nature, drugs that target DNA methylation can be developed for epigenetic therapy against EBV-associated tumours. Various methylation modes in the host and EBV genomes may also be of diagnostic and prognostic value. This review summarizes the regulatory roles of DNA methylation on the promotor of EBV gene and host genome in EBV-associated diseases, proposes the application prospect of DNA methylation in early clinical diagnosis and treatment, and provides insight into methylation-based strategies against EBV-associated diseases. Key points • Methylation of both the host and EBV genomes plays an important role in EBV-associateddiseases. • The functions of methylation of the host and EBV genomes in the occurrence and development of EBV-associated diseases are diverse. • Methylation may be a therapeutic target or biomarker in EBV-associated diseases.
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