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Epigenetic Biomarkers

Edited by Dawn DeMeo, James Flanagan, Harold Snieder, and Tomasz K. Wojdacz

New Content ItemClinical Epigenetics invites you to contribute a manuscript to our new thematic series, “Epigenetic Biomarkers”.

Epigenetic biomarkers have significantly contributed to improved understanding of the origins and progression of disease.  Moreover, increasing evidence shows that epigenetic biomarkers have potential for personalized medicine. However, routine use of epigenetic biomarkers in in-vitro diagnostics (IVD) is lagging behind the discoveries of new biomarkers. In this thematic series of Clinical Epigenetics, we discuss current progress in development of epigenetic biomarkers for clinical use in common complex diseases of ageing and welcome both original research and reviews.

The sections of the collection include:

  1. Types of epigenetic biomarkers and readiness for IVD use
    1. DNA methylation as biomarker
    2. Histone modification as biomarker
    3. Upcoming field of circulating free nucleosomes as biomarker
  2. Progress towards clinical use of biomarker

    1. Biomarkers of environmental exposures and causality of the biomarker

    2. Disease predisposition biomarkers

    3. Biomarkers used for disease detection

    4. Clinical disease prevention and management: predictive and prognostic

    5. Monitoring of chronic disease

  3. Single versus multiple biomarkers and risk scores
  4. Major stages of clinical validation of the biomarker
  5. Biomarker detection technologies suitable for IVD use and significance of bioinformatics
  6. Ethics and regulatory aspects of IVD epigenetic biomarkers

This collection of articles has not been sponsored and articles have undergone the journal’s standard peer-review process. Please find out more about our journal and its policies, here. Submission guidelines can be found here, and please submit to the series via our submission system (there will be a field for which you can indicate if you are submitting to this series).

  1. Collagen type XII alpha 1 chain (COL12A1) is associated with human cancer progression. Nevertheless, the expression pattern and the function of COL12A1 in intrahepatic cholangiocarcinoma (iCCA) remain unknown....

    Authors: Zengwei Tang, Yuan Yang, Qi Zhang and Tingbo Liang
    Citation: Clinical Epigenetics 2023 15:13
  2. Changes in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be...

    Authors: Jee Yeon Kim, Jaroslav Jelinek, Young Ho Lee, Dae Hyun Kim, Keunsoo Kang, Su Hyun Ryu, Hye Rin Moon, Kwangjo Cho, Seo Hee Rha, Jae Kwan Cha, Jean-Pierre J. Issa and Jei Kim
    Citation: Clinical Epigenetics 2023 15:11
  3. In their attempt to fulfill the wish of having children, women who suffer from fertility issues often undergo assisted reproductive technologies such as ovarian stimulation, which has been associated with adve...

    Authors: Laura Saucedo-Cuevas, Elena Ivanova, Anamaria-Cristina Herta, Felix Krueger, Katy Billooye, Johan Smitz, Gavin Kelsey and Ellen Anckaert
    Citation: Clinical Epigenetics 2023 15:9
  4. Cardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant pulmonary, cardiovascular, and neurologic complicati...

    Authors: Matthew A. Fischer, Douglas J. Chapski, Elizabeth Soehalim, Dennis J. Montoya, Tristan Grogan, Matteo Pellegrini, Hua Cai, Richard J. Shemin and Thomas M. Vondriska
    Citation: Clinical Epigenetics 2022 14:195
  5. The variation in multiple sclerosis (MS) disease severity is incompletely explained by genetics, suggesting genetic and environmental interactions are involved. Moreover, the lack of prognostic biomarkers make...

    Authors: Maria Pia Campagna, Alexandre Xavier, Rodney A. Lea, Jim Stankovich, Vicki E. Maltby, Helmut Butzkueven, Jeannette Lechner-Scott, Rodney J. Scott and Vilija G. Jokubaitis
    Citation: Clinical Epigenetics 2022 14:194
  6. Fetal overgrowth “programs” an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in pl...

    Authors: Meng-Nan Yang, Rong Huang, Tao Zheng, Yu Dong, Wen-Juan Wang, Ya-Jie Xu, Vrati Mehra, Guang-Di Zhou, Xin Liu, Hua He, Fang Fang, Fei Li, Jian-Gao Fan, Jun Zhang, Fengxiu Ouyang, Laurent Briollais…
    Citation: Clinical Epigenetics 2022 14:192
  7. Stroke is the leading cause of mortality in China. DNA methylation has essential roles in multiple diseases, but its association with stroke was barely studied. We hereby explored the association between blood...

    Authors: Chunlan Liu, Mengxia Li, Qiming Yin, Yao Fan, Chong Shen and Rongxi Yang
    Citation: Clinical Epigenetics 2022 14:191
  8. BDNF exon IV promoter methylation is a potential biomarker for treatment response to antidepressants in MDD. We have previously shown CpG-87 methylation as a successful biomarker for the prediction of non-resp...

    Authors: Hansi Pathak, Anton Borchert, Sara Garaali, Alexandra Burkert and Helge Frieling
    Citation: Clinical Epigenetics 2022 14:187
  9. Nodal mature T-cell lymphomas (nMTCL) comprises a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena, including mutations in genes that contro...

    Authors: Luís Alberto de Pádua Covas Lage, Hebert Fabrício Culler, Guilherme Carneiro Barreto, Cadiele Oliana Reichert, Débora Levy, Renata de Oliveira Costa, Vanderson Rocha and Juliana Pereira
    Citation: Clinical Epigenetics 2022 14:180
  10. Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks, is strongly associated with dietary exp...

    Authors: Kristen Kocher, Surajit Bhattacharya, Matthew S. Bramble, Daniel Okitundu-Luwa, Dieudonne Mumba Ngoyi, Desire Tshala-Katumbay and Eric Vilain
    Citation: Clinical Epigenetics 2022 14:179
  11. DNA methylation (5-mC) is being widely recognized as an alternative in the detection of sequence variants in the diagnosis of some rare neurodevelopmental and imprinting disorders. Identification of alteration...

    Authors: Robin Grolaux, Alexis Hardy, Catharina Olsen, Sonia Van Dooren, Guillaume Smits and Matthieu Defrance
    Citation: Clinical Epigenetics 2022 14:174
  12. Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). How...

    Authors: Mariateresa Casarotto, Valentina Lupato, Giorgio Giurato, Roberto Guerrieri, Sandro Sulfaro, Annamaria Salvati, Elisa D’Angelo, Carlo Furlan, Anna Menegaldo, Lorena Baboci, Barbara Montico, Irene Turturici, Riccardo Dolcetti, Salvatore Romeo, Vittorio Baggio, Stefania Corrado…
    Citation: Clinical Epigenetics 2022 14:171
  13. In recent years, non-alcoholic steatohepatitis (NASH) has become the main cause of hepatocellular carcinoma (HCC). As a means of improving the treatment of NASH-related HCCs based on early detection, this stud...

    Authors: Junko Kuramoto, Eri Arai, Mao Fujimoto, Ying Tian, Yuriko Yamada, Takuya Yotani, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Moto Fukai, Yosuke Seki, Kazunori Kasama, Nobuaki Funahashi, Haruhide Udagawa, Takao Nammo, Kazuki Yasuda…
    Citation: Clinical Epigenetics 2022 14:168
  14. The death rate of lung cancer (LC) ranks first in the world. Changes of DNA methylation in peripheral blood may be related to malignant tumors. It is necessary to explore blood-based biomarkers of methylation ...

    Authors: Yifei Fang, Yunhui Qu, Longtao Ji, Hao Sun, Jiaqi Li, Yutong Zhao, Feifei Liang, Zhi Wang, Jiao Su, Jingjing Liu, Liping Dai and Songyun Ouyang
    Citation: Clinical Epigenetics 2022 14:167
  15. We screened out several hypermethylated solute carrier (SLC) family genes in acute myeloid leukemia by reduced representation bisulfite sequencing. SLC22A3 encodes an organic cation transport protein, which is cr...

    Authors: Yu Gu, Zi-jun Xu, Jing-dong Zhou, Xiang-mei Wen, Ye Jin, Qian Yuan, Pei-hui Xia, Yuan Feng, Lei Yang, Jiang Lin and Jun Qian
    Citation: Clinical Epigenetics 2022 14:162
  16. Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic ch...

    Authors: Jonviea D. Chamberlain, Sébastien Nusslé, Laurence Chapatte, Cassandre Kinnaer, Dusan Petrovic, Sylvain Pradervand, Murielle Bochud, Sarah E. Harris, Janie Corley, Simon R. Cox and Semira Gonseth Nusslé
    Citation: Clinical Epigenetics 2022 14:155
  17. Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV te...

    Authors: Chiara Herzog, Karin Sundström, Allison Jones, Iona Evans, James E. Barrett, Jiangrong Wang, Elisa Redl, Lena Schreiberhuber, Laura Costas, Sonia Paytubi, Lukas Dostalek, Michal Zikan, David Cibula, Gaby Sroczynski, Uwe Siebert, Joakim Dillner…
    Citation: Clinical Epigenetics 2022 14:150
  18. Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-s...

    Authors: Kanto Shozu, Syuzo Kaneko, Norio Shinkai, Ai Dozen, Hirofumi Kosuge, Makoto Nakakido, Hidenori Machino, Ken Takasawa, Ken Asada, Masaaki Komatsu, Kouhei Tsumoto, Shin-Ichi Ohnuma and Ryuji Hamamoto
    Citation: Clinical Epigenetics 2022 14:147
  19. Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana’s effect on aging remains understudied ...

    Authors: Drew R. Nannini, Yinan Zheng, Brian T. Joyce, Tao Gao, Lei Liu, David R. Jacobs Jr., Pamela Schreiner, Chunyu Liu, Steve Horvath, Ake T. Lu, Kristine Yaffe, Stephen Sidney, Philip Greenland, Donald M. Lloyd-Jones and Lifang Hou
    Citation: Clinical Epigenetics 2022 14:134
  20. 5-Hydroxymethylcytosine (5hmC), an important DNA epigenetic modification, plays a vital role in tumorigenesis, progression and prognosis in many cancers. Diffuse large B cell lymphoma (DLBCL) can involve almos...

    Authors: Ye Shen, Jinping Ou, Bo He, Jinmin Yang, Huihui Liu, Lihong Wang, Bingjie Wang, Liang Gao, Chengqi Yi, Jinying Peng and Xinan Cen
    Citation: Clinical Epigenetics 2022 14:126
  21. The neurological course after stroke is highly variable and is determined by demographic, clinical and genetic factors. However, other heritable factors such as epigenetic DNA methylation could play a role in ...

    Authors: Natalia Cullell, Carolina Soriano-Tárraga, Cristina Gallego-Fábrega, Jara Cárcel-Márquez, Elena Muiño, Laia Llucià-Carol, Miquel Lledós, Manel Esteller, Manuel Castro de Moura, Joan Montaner, Anna Rosell, Pilar Delgado, Joan Martí-Fábregas, Jerzy Krupinski, Jaume Roquer, Jordi Jiménez-Conde…
    Citation: Clinical Epigenetics 2022 14:124
  22. DNA methylation-regulated genes have been demonstrated as the crucial participants in the occurrence of coronary heart disease (CHD). The machine learning based on DNA methylation-regulated genes has tremendou...

    Authors: Xiaokang Zhang, Chen Wang, Dingdong He, Yating Cheng, Li Yu, Daoxi Qi, Boyu Li and Fang Zheng
    Citation: Clinical Epigenetics 2022 14:122
  23. Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed to...

    Authors: Peilong Li, Shibiao Liu, Lutao Du, Ghazal Mohseni, Yi Zhang and Chuanxin Wang
    Citation: Clinical Epigenetics 2022 14:118
  24. DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. How...

    Authors: Jie Qi, Yue Shi, Yezhen Tan, Qi Zhang, Jianye Zhang, Jilu Wang, Cong Huang and Weimin Ci
    Citation: Clinical Epigenetics 2022 14:117
  25. Lung cancer patients are diagnosed at late stages when curative treatments are no longer possible; thus, molecular biomarkers for noninvasive detection are urgently needed. In this sense, we previously identif...

    Authors: Cora Palanca-Ballester, David Hervas, Maria Villalba, Teresa Valdes-Sanchez, Diana Garcia, Maria Isabel Alcoriza-Balaguer, Marta Benet, Raquel Martinez-Tomas, Andres Briones-Gomez, Jose Galbis-Caravajal, Alfonso Calvo, Oscar Juan, Agustin Lahoz, Enrique Cases and Juan Sandoval
    Citation: Clinical Epigenetics 2022 14:116
  26. Over the past decade, bioethicists, legal scholars and social scientists have started to investigate the potential implications of epigenetic research and technologies on medicine and society. There is growing...

    Authors: Charles Dupras, Terese Knoppers, Nicole Palmour, Elisabeth Beauchamp, Stamatina Liosi, Reiner Siebert, Alison May Berner, Stephan Beck, Ian Charest and Yann Joly
    Citation: Clinical Epigenetics 2022 14:110
  27. DNA methylation in the human genome is established and maintained by DNA methyltransferases (DNMTs). DNMT isoforms show differential expression by cell lineage and during development, but much remains to be el...

    Authors: Chanachai Sae-Lee, Timothy M. Barrow, Elena Colicino, Si Ho Choi, Yoana Rabanal-Ruiz, Daniel Green, Viktor I. Korolchuk, John C. Mathers and Hyang-Min Byun
    Citation: Clinical Epigenetics 2022 14:103
  28. DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavior...

    Authors: Kyeezu Kim, Yinan Zheng, Brian T. Joyce, Hongmei Jiang, Philip Greenland, David R. Jacobs Jr., Kai Zhang, Lei Liu, Norrina B. Allen, John T. Wilkins, Sarah N. Forrester, Donald M. Lloyd-Jones and Lifang Hou
    Citation: Clinical Epigenetics 2022 14:85
  29. Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have bee...

    Authors: Sara Sammallahti, M. Elisabeth Koopman-Verhoeff, Anne-Claire Binter, Rosa H. Mulder, Alba Cabré-Riera, Tuomas Kvist, Anni L. K. Malmberg, Giancarlo Pesce, Sabine Plancoulaine, Jonathan A. Heiss, Sheryl L. Rifas-Shiman, Stefan W. Röder, Anne P. Starling, Rory Wilson, Kathrin Guerlich, Kristine L. Haftorn…
    Citation: Clinical Epigenetics 2022 14:83
  30. Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of my...

    Authors: Jia Li, Tingting Hong, Yue Wei, Lei Guo, Minjung Lee, Hui Yang, Caleb Class, Yaling Yang, Xiaoqiong Wang, Hua He, Stefan Siwko, M. James You, Yubin Zhou, Guillermo Garcia-Manero and Yun Huang
    Citation: Clinical Epigenetics 2022 14:81
  31. Ovarian cancer (OC) is a highly lethal gynecologic cancer, and it is hard to diagnose at an early stage. Clinically, there are no ovarian cancer-specific markers for early detection. Here, we demonstrate the u...

    Authors: Huaiwu Lu, Yunyun Liu, Jingyu Wang, Shaliu Fu, Lingping Wang, Chunxian Huang, Jing Li, Lingling Xie, Dongyan Wang, Dan Li, Hui Zhou and Qunxian Rao
    Citation: Clinical Epigenetics 2022 14:74
  32. DNA methylation biomarkers for early detection, risk stratification and treatment response in cancer have been of great interest over the past decades. Nevertheless, clinical implementation of these biomarkers...

    Authors: Maartje Massen, Kim Lommen, Kim A. D. Wouters, Johan Vandersmissen, Wim van Criekinge, James G. Herman, Veerle Melotte, Leo J. Schouten, Manon van Engeland and Kim M. Smits
    Citation: Clinical Epigenetics 2022 14:56
  33. Multiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers have not been thoroughly validated and therefore are still not...

    Authors: Šárka Šestáková, Ela Cerovská, Cyril Šálek, Dávid Kundrát, Ivana Ježíšková, Adam Folta, Jiří Mayer, Zdeněk Ráčil, Petr Cetkovský and Hana Remešová
    Citation: Clinical Epigenetics 2022 14:22
  34. Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant compli...

    Authors: Iacopo Cristoferi, Tommaso Antonio Giacon, Karin Boer, Myrthe van Baardwijk, Flavia Neri, Manuela Campisi, Hendrikus J. A. N. Kimenai, Marian C. Clahsen - van Groningen, Sofia Pavanello, Lucrezia Furian and Robert C. Minnee
    Citation: Clinical Epigenetics 2022 14:20
  35. Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age accel...

    Authors: Rhona A. Beynon, Suzanne M. Ingle, Ryan Langdon, Margaret May, Andy Ness, Richard M. Martin, Matthew Suderman, Kate Ingarfield, Riccardo E. Marioni, Daniel L. McCartney, Tim Waterboer, Michael Pawlita, Caroline Relton, George Davey Smith and Rebecca C. Richmond
    Citation: Clinical Epigenetics 2022 14:1
  36. Circulating tumor DNA (ctDNA) is a promising diagnostic and prognostic marker for many cancers and has been actively investigated in recent years. Previous studies have already demonstrated the potential use o...

    Authors: Wu-Hao Lin, Jian Xiao, Zi-Yi Ye, Da-Liang Wei, Xiao-Hui Zhai, Rui-Hua Xu, Zhao-Lei Zeng and Hui-Yan Luo
    Citation: Clinical Epigenetics 2021 13:232
  37. Metformin and weight loss relationships with epigenetic age measures—biological aging biomarkers—remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese br...

    Authors: Jamaji C. Nwanaji-Enwerem, Felicia Fei-Lei Chung, Lars Van der Laan, Alexei Novoloaca, Cyrille Cuenin, Harriet Johansson, Bernardo Bonanni, Alan E. Hubbard, Martyn T. Smith, Sheri J. Hartman, Andres Cardenas, Dorothy D. Sears and Zdenko Herceg
    Citation: Clinical Epigenetics 2021 13:224
  38. Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression a...

    Authors: Jian Zhou, Tong Cheng, Xing Li, Jie Hu, Encheng Li, Ming Ding, Rulong Shen, John P. Pineda, Chun Li, Shaohua Lu, Hongyu Yu, Jiayuan Sun, Wenbin Huang, Xiaonan Wang, Han Si, Panying Shi…
    Citation: Clinical Epigenetics 2021 13:220
  39. The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often ...

    Authors: Ashna Maredia, David Guzzardi, Mohammad Aleinati, Fatima Iqbal, Arshroop Khaira, Aiswarya Madhu, Xuemei Wang, Alex J. Barker, Patrick M. McCarthy, Paul W. M. Fedak and Steven C. Greenway
    Citation: Clinical Epigenetics 2021 13:147
  40. Increasing evidence linking epigenetic mechanisms and different diseases, including cancer, has prompted in the last 15 years the investigation of histone post-translational modifications (PTMs) in clinical sa...

    Authors: Roberta Noberini, Evelyn Oliva Savoia, Stefania Brandini, Francesco Greco, Francesca Marra, Giovanni Bertalot, Giancarlo Pruneri, Liam A. McDonnell and Tiziana Bonaldi
    Citation: Clinical Epigenetics 2021 13:145
  41. Current risk models for renal cell carcinoma (RCC) based on clinicopathological factors are sub-optimal in accurately identifying high-risk patients. Here, we perform a head-to-head comparison of previously pu...

    Authors: S. C. Joosten, S. N. O. Odeh, A. Koch, N. Buekers, M. J. B. Aarts, M. M. L. L. Baldewijns, L. Van Neste, S. van Kuijk, L. J. Schouten, P. A. van den Brandt, V. C. Tjan-Heijnen, M. van Engeland and K. M. Smits
    Citation: Clinical Epigenetics 2021 13:103