DNA Hydroxymethylation in Smoking-Associated Cancers

Besaratinia, Ahmad; Caceres, Amanda; Tommasi, Stefania

doi:10.3390/ijms23052657

Cited by 12 publications

(5 citation statements)

References 218 publications

(459 reference statements)

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“…Moreover, the lack of differences between sexes in the expression of SURVIVIN/BIRC5 in blood leukocytes could be due to the relatively small sample size in the human cohort. Another limitation could be the lack of data about other cancer risk factors, such as tobacco [ 59 , 60 ] or saturated fats [ 59 , 61 ] consumption among study patients, which could be factors that influenced the results. However, the trend in gene expression was similar to that observed in the animal model, suggesting that smoking was not a relevant confounding factor in this analysis.…”

Section: Discussionmentioning

confidence: 99%

Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

Izquierdo

Carreira

Rodríguez-Carnero

et al. 2022

IJMS

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Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) show clear evidence of sexual dimorphism, with a significantly higher incidence in males. Among the determining factors that could explain this sex-based difference, the specific distribution of fat by sex has been suggested as a primary candidate, since obesity is a relevant risk factor. In this context, obesity, considered a low-grade chronic inflammatory pathology and responsible for the promotion of liver disease, could lead to sexual dimorphism in the expression profile of genes related to tumor development. When we compared the expression levels of genes associated with the early stages of carcinogenesis in the liver between male and female diet-induced obesity (DIO) rats, we observed that the expression pattern was similar in obese male and female animals. Interestingly, the SURVIVIN/BIRC5 oncogene showed a higher expression in male DIO rats than in female DIO and lean rats. This trend related to sexual dimorphism was observed in leukocytes from patients with obesity, although the difference was not statistically significant. In conclusion, this study evidenced a similar pattern in the expression of most carcinogenesis-related genes in the liver, except SUVIVIN/BIRC5, which could be a predictive biomarker of liver carcinogenesis predisposition in male patients with obesity.

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Section: Discussionmentioning

confidence: 99%

Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

Izquierdo

Carreira

Rodríguez-Carnero

et al. 2022

IJMS

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“…Of the three, aberrant DNA methylation is the most extensively studied epigenetic alteration [129,132]. Relatedly, studies on DNA hydroxymethylation and BPA exposure are also beginning to emerge [136][137][138][139][140][141][142]. Collectively, studies on the epigenetic effects of BPA have been performed in cell cultures (in vitro), experimental animals (in vivo), and human populations.…”

Section: Epigenetic Effects Of Bpamentioning

confidence: 99%

The State of Research and Weight of Evidence on the Epigenetic Effects of Bisphenol A

Besaratinia

2023

IJMS

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Bisphenol A (BPA) is a high-production-volume chemical with numerous industrial and consumer applications. BPA is extensively used in the manufacture of polycarbonate plastics and epoxy resins. The widespread utilities of BPA include its use as internal coating for food and beverage cans, bottles, and food-packaging materials, and as a building block for countless goods of common use. BPA can be released into the environment and enter the human body at any stage during its production, or in the process of manufacture, use, or disposal of materials made from this chemical. While the general population is predominantly exposed to BPA through contaminated food and drinking water, non-dietary exposures through the respiratory system, integumentary system, and vertical transmission, as well as other routes of exposure, also exist. BPA is often classified as an endocrine-disrupting chemical as it can act as a xenoestrogen. Exposure to BPA has been associated with developmental, reproductive, cardiovascular, neurological, metabolic, or immune effects, as well as oncogenic effects. BPA can disrupt the synthesis or clearance of hormones by binding and interfering with biological receptors. BPA can also interact with key transcription factors to modulate regulation of gene expression. Over the past 17 years, an epigenetic mechanism of action for BPA has emerged. This article summarizes the current state of research on the epigenetic effects of BPA by analyzing the findings from various studies in model systems and human populations. It evaluates the weight of evidence on the ability of BPA to alter the epigenome, while also discussing the direction of future research.

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“…Notably, aberrant DNA hydroxymethylation is also considered one of the earliest events in urothelial carcinomas (16,17). A global loss of 5-hmC has been observed in both UBC and UBC cell lines compared to controls or adjacent tissues (15). Therefore, similar to the conventional DNA methylation level measured based on bisul te treatment, the hydroxymethylation level is also conceived to be a promising biomarker for UBC detection, especially in the repetitive surveillance of recurrent UBC.…”

Section: Introductionmentioning

confidence: 99%

Integrative multi-Omics analysis depicts the methylome and hydroxymethylome of recurrent bladder cancers and identifies biomarkers for predicting PD-L1 expression

Han

Dong

Pang

et al. 2023

Preprint

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Background: Urinary bladder cancer is one of the most common malignancies of the urinary tract; however, the mechanism of its high recurrence and responses to immunotherapy remains unclear, resulting in difficulties in clinical outcome prediction. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly investigated as biomarkers for diagnostic or prognostic predictions. However, little is known regarding hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results. Methods: Here, we used a multi-omics approach to provide the genome, transcriptome, methylome, and hydroxymethylome landscape of both primary and recurrent bladder cancers. Results: By whole exome sequencing, we identified driver mutations that are involved in the UBC development, such as FGFR3, KDMTA and KDMT2C. However, few of these driver mutations are associated with the recurrence or the PD-L1 down-regulation in UBC. By integrating RRBS and oxRRBS-seq data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a serial of 5mC hypomethylation DMRs in the gene body of NFATC1, a gene that is highly involved in the T-cell immune response, in bladder cancer samples with high expression of PD-L1. And since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq based markers which combine the 5mC and 5hmC signals, attenuate the cancer-related signals and therefore are not optimal to be used as clinical biomarkers. Conclusions: By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved than genetic mutations in the recurrence and PD-L1 regulation of UBC. In addition, as a proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC level by bisulfite-based method will compromise the prediction accuracy of epigenetic biomarkers.

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DNA Hydroxymethylation in Smoking-Associated Cancers

Cited by 12 publications

References 218 publications

Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease

The State of Research and Weight of Evidence on the Epigenetic Effects of Bisphenol A

Integrative multi-Omics analysis depicts the methylome and hydroxymethylome of recurrent bladder cancers and identifies biomarkers for predicting PD-L1 expression

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