Dataset Information

DNA methylation profiling of CD04⁺/CD08⁺ T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

ABSTRACT:

Background

DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage.

Material and methods

We investigated DNA methylome by RRBS in CD04⁺ and CD08⁺ T cells from healthy subjects (HS) to pre-diabetics (Pre-Diab) and type 2 diabetic (T2D) patients to identify early biomarkers of glucose impairment and vascular damage. Our cross-sectional study enrolled 14 individuals from HS state to increasing hyperglycemia (pilot study, PIRAMIDE trial, NCT03792607).

Results

Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04⁺ T cells whereas CD08⁺ T showed an opposite trend. Moreover, DMRs overlapping between Pre-Diab and T2D patients were mostly hypermethylated in both T cells. Interestingly, SPARC was the most hypomethylated gene in Pre-Diab and its methylation level gradually decreased in T2D patients. Besides, SPARC showed a significant positive correlation with DBP (+0.76), HDL (+0.54), Creatinine (+0.83), LVDd (+0.98), LVSD (+0.98), LAD (+0.98), LVPWd (+0.84), AODd (+0.81), HR (+0.72), Triglycerides (+0.83), LAD (+0.69) and AODd (+0.52) whereas a negative correlation with Cholesterol (-0.52) and LDL (-0.71) in T2D.

Conclusion

SPARC hypomethylation in CD08⁺ T cells may be a useful biomarker of vascular complications in Pre-Diab with a possible role for primary prevention warranting further multicenter clinical trials to validate our findings.

SUBMITTER: Benincasa G

PROVIDER: S-EPMC7645316 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

DNA methylation profiling of CD04<sup>+</sup>/CD08<sup>+</sup> T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Benincasa Giuditta G Franzese Monica M Schiano Concetta C Marfella Raffaele R Miceli Marco M Infante Teresa T Sardu Celestino C Zanfardino Mario M Affinito Ornella O Mansueto Gelsomina G Sommese Linda L Nicoletti Giovanni Francesco GF Salvatore Marco M Paolisso Giuseppe G Napoli Claudio C

Annals of medicine and surgery (2012) 20201020

<h4>Background</h4>DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage.<h4>Material and methods</h4>We investigated DNA methylome by RRBS in CD04<sup>+</sup> and CD08<sup>+</sup> T cells from healthy subjects (HS) to pre-diabetics (Pre-Diab) and type 2 diabetic (T2D) patients to identify early biomarkers of glucose impairment and vascular damage. Our cross-sectional study enrolled 14 individuals from HS state to increa ...[more]

PMID: 33194177

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Project description:DNA methylation is a vital early step in carcinogenesis. Most findings of aberrant DNA methylation in head and neck squamous cell carcinomas (HNSCC) are array based with limited coverage and resolution, and mainly explored by human papillomavirus (HPV) status, ignoring the high heterogeneity of this disease. In this study, we performed whole-genome bisulfite sequencing on a well-studied HNSCC cohort (n = 36) and investigated the methylation changes between fine-scaled HNSCC subtypes in relation to genomic instability, repetitive elements, gene expression, and key carcinogenic pathways. The previously observed hypermethylation phenotype in HPV-positive (HPV+) tumors compared with HPV-negative tumors was robustly present in the immune-strong (IMU) HPV+ subtype but absent in the highly keratinized (KRT) HPV+ subtype. Methylation levels of IMU tumors were significantly higher in repetitive elements, and methylation showed a significant correlation with genomic stability, consistent with the IMU subtype having more genomic stability and better prognosis. Expression quantitative trait methylation (cis-eQTM) analysis revealed extensive functionally-relevant differences, and differential methylation pathway analysis recapitulated gene expression pathway differences between subtypes. Consistent with their characteristics, KRT and HPV-negative tumors had high regulatory potential for multiple regulators of keratinocyte differentiation, which positively correlated with an expression-based keratinization score. Together, our findings revealed distinct mechanisms of carcinogenesis between subtypes in HPV+ HNSCC and uncovered previously ignored epigenomic differences and clinical implications, illustrating the importance of fine-scale subtype analysis in cancer.SignificanceThis study revealed that the previously observed hypermethylation of HPV(+) HNSCC is due solely to the IMU subtype, illustrating the importance of fine-scale subtype analysis in such a heterogeneous disease. Particularly, IMU has significantly higher methylation of transposable elements, which can be tested as a prognosis biomarker in future translational studies.

Dataset Information

DNA methylation profiling of CD04⁺/CD08⁺ T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Background

Material and methods

Results

Conclusion

Publications

DNA methylation profiling of CD04<sup>+</sup>/CD08<sup>+</sup> T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Background

Material and methods

Results

Conclusion

Publications

DNA methylation profiling of CD04<sup>+</sup>/CD08<sup>+</sup> T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

DNA methylation profiling of CD04⁺/CD08⁺ T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.