Inhibitory immune checkpoints PDCD-1 and LAG-3 hypermethylation may reduce the risk of colorectal cancer
| العنوان: | Inhibitory immune checkpoints PDCD-1 and LAG-3 hypermethylation may reduce the risk of colorectal cancer |
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| المؤلفون: | Tian Tian, Yashuang Zhao, Hao Huang, Jing Xu, Guiyu Wang, Jinming Fu, Lei Zhang, Ding Zhang, Ying Liu, Hongru Sun, Yuanyuan Zhang |
| المصدر: | Molecular Medicine, Vol 27, Iss 1, Pp 1-10 (2021) Molecular Medicine |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Oncology, Colorectal cancer, Programmed Cell Death 1 Receptor, Biochemistry, Epigenesis, Genetic, Workflow, Risk Factors, Databases, Genetic, Medicine, Genetics (clinical), Aged, 80 and over, DNA methylation, Methylation, Middle Aged, Lymphocyte Activation Gene 3 Protein, Gene Expression Regulation, Neoplastic, Immunosurveillance, CpG site, Molecular Medicine, Female, Disease Susceptibility, PDCD-1, Colorectal Neoplasms, Research Article, Adult, medicine.medical_specialty, RM1-950, QD415-436, Lower risk, Risk Assessment, Peripheral blood leukocyte, Immune system, Antigens, CD, LAG-3, Internal medicine, Biomarkers, Tumor, Genetics, Humans, Molecular Biology, Aged, business.industry, Gene Expression Profiling, Computational Biology, Immune Checkpoint Proteins, medicine.disease, Molecular medicine, Case-Control Studies, CpG Islands, Therapeutics. Pharmacology, Transcriptome, business |
| الوصف: | Background Changes in DNA methylation of immunosuppressive checkpoints may impact express and consequently affect antigen processing and presentation by tumor cells and facilitates evasion of immunosurveillance and lead to colorectal cancer (CRC). This study is to investigate the effect of PDCD-1, LAG-3 methylation statuses in peripheral blood leukocytes on CRC risk. Methods GSE51032 dataset from Gene Expression Omnibus comprised of 166 CRC patients and 424 normal samples was used to identify significantly differentially methylated CpG sites of the two genes. A case–control study with 390 CRC patients and 397 cancer-free controls was carried out to validate the relationship between the methylation levels of the two genes and CRC susceptibility and then estimated their interactions with environmental factors on CRC risk. Results In the GSE51032 dataset, cg06291111 (PDCD-1) and cg10191002 (LAG-3) were screened as the candidate CpG sites for the following study. There were significant associations between hypermethylation of PDCD-1 and LAG-3 and lower risk of CRC (ORadj = 0.322, 95% CI 0.197–0.528; ORadj = 0.666, 95% CI 0.446–0.5996, respectively). Moreover, the results in case–control study showed similar trend, that hypermethylation of PDCD-1 and LAG-3 were associated with lower CRC risk (ORadj = 0.448, 95% CI 0.322–0.622; ORadj = 0.417, 95% CI 0.301–0.578, respectively). A synergistic interaction between LAG-3 hypermethylation and intake of eggs on CRC risk was observed. There were combination effects between hypermethylation of PDCD-1 and LAG-3 and environmental factors on CRC risk. Conclusions PDCD-1 and LAG-3 may potentially serve as blood-based predictive biomarkers for CRC risk. |
| اللغة: | English |
| تدمد: | 1528-3658 1076-1551 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7fce0f0a2e1f1bbead13b796ea4a2d1Test https://doaj.org/article/60cbc5aee2e646e98917e4df8a0c9c49Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c7fce0f0a2e1f1bbead13b796ea4a2d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15283658 10761551 |
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