DNA methylation drives a new path in gastric cancer early detection: Current impact and prospects

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Abstract

Gastric cancer (GC) is one of the most common and deadly cancers worldwide. Early detection offers the best chance for curative treatment and reducing its mortality. However, the optimal population-based early screening for GC remains unmet. Aberrant DNA methylation occurs in the early stage of GC, exhibiting cancer-specific genetic and epigenetic changes, and can be detected in the media such as blood, gastric juice, and feces, constituting a valuable biomarker for cancer early detection. Furthermore, DNA methylation is a stable epigenetic alteration, and many innovative methods have been developed to quantify it rapidly and accurately. Nonetheless, large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking, precluding their implementation in clinical practice. In conclusion, after a critical analysis of the recent existing literature, we summarized the evolving roles of DNA methylation during GC occurrence, expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC, and discussed its challenges and prospects in clinical applications.

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Cancer statistics, 2022

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

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DNA methylation age of human tissues and cell types

Steve Horvath, Ilias Lagkouvardos (2014)

Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.

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DNA methylation and its basic function.

Lisa Moore, Thuc Le, Guoping Fan (2013)

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. During development, the pattern of DNA methylation in the genome changes as a result of a dynamic process involving both de novo DNA methylation and demethylation. As a consequence, differentiated cells develop a stable and unique DNA methylation pattern that regulates tissue-specific gene transcription. In this chapter, we will review the process of DNA methylation and demethylation in the nervous system. We will describe the DNA (de)methylation machinery and its association with other epigenetic mechanisms such as histone modifications and noncoding RNAs. Intriguingly, postmitotic neurons still express DNA methyltransferases and components involved in DNA demethylation. Moreover, neuronal activity can modulate their pattern of DNA methylation in response to physiological and environmental stimuli. The precise regulation of DNA methylation is essential for normal cognitive function. Indeed, when DNA methylation is altered as a result of developmental mutations or environmental risk factors, such as drug exposure and neural injury, mental impairment is a common side effect. The investigation into DNA methylation continues to show a rich and complex picture about epigenetic gene regulation in the central nervous system and provides possible therapeutic targets for the treatment of neuropsychiatric disorders.

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Author and article information

Contributors

Lutao Du

Chuanxin Wang

Journal

Journal ID (nlm-ta): Genes Dis

Journal ID (iso-abbrev): Genes Dis

Title: Genes & Diseases

Publisher: Chongqing Medical University

ISSN (Print): 2352-4820

ISSN (Electronic): 2352-3042

Publication date PMC-release: 30 March 2023

Publication date Collection: March 2024

Publication date (Electronic): 30 March 2023

Volume: 11

Issue: 2

Pages: 847-860

Affiliations

[a ]Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, China

[b ]Department of Clinical Laboratory, Fuling Hospital, Chongqing University, Chongqing 402774, China

[c ]Suzhou Research Institute of Shandong University, Suzhou, Jiangsu 215123, China

[d ]Department of Biochemistry and Molecular Biology, Shandong University School of Basic Medical Sciences, Jinan, Shandong 250012, China

[e ]Shandong Engineering & Technology Research Center for Tumor Marker Detection, Jinan, Shandong 250033, China

[f ]Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, Shandong 250033, China

Author notes

[∗ ]Corresponding author. Department of Clinical Laboratory, The Second Hospital of Shandong University, No. 247 Beiyuan Street, Jinan, Shandong 250033, China. lutaodu@ 123456sdu.edu.cn cxwang@ 123456sdu.edu.cn

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S2352-3042(23)00090-9

DOI: 10.1016/j.gendis.2023.02.038

PMC ID: 10491876

PubMed ID: 37692483

SO-VID: 9e60b440-d421-4d1e-9867-985303fd8dbb

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

DNA methylation drives a new path in gastric cancer early detection: Current impact and prospects

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Genes & Diseases

Most cited references 142

Cancer statistics, 2022

DNA methylation age of human tissues and cell types

DNA methylation and its basic function.

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