Clinical Epigenetics最新文献

{"title":"DNA hypermethylation driven by DNMT1 and DNMT3A favors tumor immune escape contributing to the aggressiveness of adrenocortical carcinoma.","authors":"Gwenneg Kerdivel,&nbsp;Floriane Amrouche,&nbsp;Marie-Ange Calmejane,&nbsp;Floriane Carallis,&nbsp;Juliette Hamroune,&nbsp;Constanze Hantel,&nbsp;Jérôme Bertherat,&nbsp;Guillaume Assié,&nbsp;Valentina Boeva","doi":"10.1186/s13148-023-01534-5","DOIUrl":"https://doi.org/10.1186/s13148-023-01534-5","url":null,"abstract":"<p><strong>Background: </strong>Adrenocortical carcinoma is rare and aggressive endocrine cancer of the adrenal gland. Within adrenocortical carcinoma, a recently described subtype characterized by a CpG island methylator phenotype (CIMP) has been associated with an especially poor prognosis. However, the drivers of CIMP remain unknown. Furthermore, the functional relation between CIMP and poor clinical outcomes of patients with adrenocortical carcinoma stays elusive.</p><p><strong>Results: </strong>Here, we show that CIMP in adrenocortical carcinoma is linked to the increased expression of DNA methyltransferases DNMT1 and DNMT3A driven by a gain of gene copy number and cell hyperproliferation. Importantly, we demonstrate that CIMP contributes to tumor aggressiveness by favoring tumor immune escape. This effect could be at least partially reversed by treatment with the demethylating agent 5-azacytidine.</p><p><strong>Conclusions: </strong>In sum, our findings suggest that co-treatment with demethylating agents might enhance the efficacy of immunotherapy and could represent a novel therapeutic approach for patients with high CIMP adrenocortical carcinoma.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"121"},"PeriodicalIF":5.7,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9943494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAX1 hypomethylation as a prognostic biomarker for radioresistance of cervical cancer.","authors":"Xuanxuan Li,&nbsp;Huan Liu,&nbsp;Xue Zhou,&nbsp;Yangying Zhou,&nbsp;Yu Zhang,&nbsp;Yu-Ligh Liou,&nbsp;Manting Zeng,&nbsp;Hong Zhu","doi":"10.1186/s13148-023-01538-1","DOIUrl":"https://doi.org/10.1186/s13148-023-01538-1","url":null,"abstract":"<p><strong>Background: </strong>PAX1 gene methylation plays an important role in the development of cervical cancer. However, its prognostic value after radiotherapy for locally advanced cervical cancer is unknown, so this study aimed to investigate the value of PAX1 gene methylation for predicting the sensitivity of radiotherapy for cervical cancer.</p><p><strong>Methods: </strong>We selected 125 patients with primary cervical cancer who underwent concurrent chemo-radiotherapy as the study population, quantitative methylation-specific polymerase chain reaction (QMSP) was used for detecting PAX1 methylation status of cervical exfoliated cells. Logistic regression model was used to analyze the risk factors associated with the short-term efficacy and to establish a prediction model of radiotherapy sensitivity based on PAX1 gene methylation. Cell viability after radiation of Hela and SiHa cells transfected with PAX1 or control vector was evaluated by CCK8. Furthermore, RNA-Seq analyses identified different expressed genes (DEGs) in PAX1 overexpressed SiHa cells. Gene Ontology (GO) and pathway enrichment analysis was carried out to determine the biological function of DEGs.</p><p><strong>Results: </strong>PAX1 methylation level was associated with HPV16/18-positive rate. PAX1 hypomethylation was found to be a risk factor for tumor residual after chemo-radiotherapy. A nomogram containing the risk factors for PAX1 methylation status, lymph node metastasis, pathological type and tumor size was further constructed to predict the probability of tumor residual after chemo-radiotherapy (AUC = 0.823, 95% CI 0.736-0.910). High PAX1 protein level was more likely to cause radioresistance in both Hela and SiHa cells. Transcriptomic sequencing of PAX1 overexpressed and control cells identified 615 differentially expressed genes, and GO enrichment analysis suggested that PAX1 may be involved in the regulation of signaling receptor activity and response to viruses.</p><p><strong>Conclusion: </strong>PAX1 hypomethylation status could be used as a promising biomarker to predict radioresistance in cervical cancer. This further provides a new idea for the individualized treatment strategy of simultaneous radiotherapy for cervical cancer.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"123"},"PeriodicalIF":5.7,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypomethylation of ABCG1 in peripheral blood as a potential marker for the detection of coronary heart disease.","authors":"Jialie Jin,&nbsp;Xiaojing Zhao,&nbsp;Chao Zhu,&nbsp;Mengxia Li,&nbsp;Jinxin Wang,&nbsp;Yao Fan,&nbsp;Chunlan Liu,&nbsp;Chong Shen,&nbsp;Rongxi Yang","doi":"10.1186/s13148-023-01533-6","DOIUrl":"https://doi.org/10.1186/s13148-023-01533-6","url":null,"abstract":"<p><strong>Background: </strong>Novel molecular biomarkers for the risk assessment and early detection of coronary heart disease (CHD) are urgently needed for disease prevention. Altered methylation of ATP-binding cassette subfamily G member 1 (ABCG1) has been implicated in CHD but was mostly studied in Caucasians. Exploring the potential relationship between ABCG1 methylation in blood and CHD among the Chinese population would yield valuable insights.</p><p><strong>Methods: </strong>Peripheral blood samples were obtained from a case-control study (287 CHD patients vs. 277 controls) and a prospective nested case-control study (171 CHD patients and 197 matched controls). DNA extraction and bisulfite-specific PCR amplification techniques were employed for sample processing. Quantitative assessment of methylation levels was conducted using mass spectrometry. Statistical analyses involved the utilization of logistic regression and nonparametric tests.</p><p><strong>Results: </strong>We found hypomethylation of ABCG1 in whole blood was associated with the risk of CHD in both studies, which was enhanced in heart failure (HF) patients, female and younger subjects. When combined with baseline characteristics, altered ABCG1 methylation showed improved predictive effect for differentiating CHD cases, ischemic cardiomyopathy (ICM) cases, younger than 60 years CHD cases, and female CHD cases from healthy controls (area under the curve (AUC) = 0.68, 0.71, 0.74, and 0.73, respectively).</p><p><strong>Conclusions: </strong>We demonstrated a robust link between ABCG1 hypomethylation in whole blood and CHD risk in the Chinese population and provided novel evidence indicating that aberrant ABCG1 methylation in peripheral blood can serve as an early detection biomarker for CHD patients.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"120"},"PeriodicalIF":5.7,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9996172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide discovery of circulating cell-free DNA methylation biomarkers for colorectal cancer detection.","authors":"Qingxiao Fang,&nbsp;Ziming Yuan,&nbsp;Hanqing Hu,&nbsp;Weiyuan Zhang,&nbsp;Guiyu Wang,&nbsp;Xishan Wang","doi":"10.1186/s13148-023-01518-5","DOIUrl":"https://doi.org/10.1186/s13148-023-01518-5","url":null,"abstract":"<p><strong>Background: </strong>Colorectal polyp is known a precursor of colorectal cancer (CRC) that holds an increased risk for progression to CRC. Circulating cell-free DNA (cfDNA) methylation has shown favorable performance in the detection and monitoring the malignant progression in a variety of cancers.</p><p><strong>Results: </strong>To discover cfDNA methylation markers for the diagnosis of CRC, we first performed a genome-wide analysis between eight CRC and eight polyp tissues using the Infinium HumanMethylationEPIC BeadChip. We identified 7008 DMCs, and after filtering, we validated 39 DMCs by MethylTarget sequencing in 62 CRC and 56 polyp tissues. A panel of four CpGs (cg04486886, cg06712559, cg13539460, and cg27541454) was selected as the methylation marker in tissue by LASSO and random forest models. A diagnosis prediction model was built based on the four CpGs, and the methylation diagnosis score (md-score) can effectively discriminate tissues with CRC from polyp patients (AUROC > 0.9). Finally, the cg27541454 was confirmed hypermethylated in CRC (AUC = 0.85) in the plasma validation cohort.</p><p><strong>Conclusions: </strong>Our findings suggest that the md-score could robustly detect CRC from polyp tissues, and cg27541454 may be a promising candidate noninvasive biomarker for CRC early diagnosis.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"119"},"PeriodicalIF":5.7,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating NPTX2 methylation as a non-invasive biomarker for prognosis and monitoring of metastatic pancreatic cancer.","authors":"María Victoria García-Ortiz, Pablo Cano-Ramírez, Marta Toledano-Fonseca, María Teresa Cano, Elizabeth Inga-Saavedra, Rosa María Rodríguez-Alonso, Silvia Guil-Luna, María Auxiliadora Gómez-España, Antonio Rodríguez-Ariza, Enrique Aranda","doi":"10.1186/s13148-023-01535-4","DOIUrl":"10.1186/s13148-023-01535-4","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is the most lethal cancer with a dismal prognosis mainly due to diagnosis at advanced stage and ineffective treatments. CA19-9 levels and computed tomography (CT) imaging are the main standard criteria for evaluating disease progression and treatment response. In this study we explored liquid biopsy-based epigenetic biomarkers for prognosis and monitoring disease in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).</p><p><strong>Methods: </strong>Plasma samples were collected from 44 mPDAC patients at the time of diagnosis, and in 15 of them, additional samples were obtained during follow-up of the disease. After cell-free DNA (cfDNA), isolation circulating levels of methylated NPTX2, SPARC, BMP3, SFRP1 and TFPI2 genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of RAS mutations in cfDNA, and CA19-9 was measured using standard techniques.</p><p><strong>Results: </strong>NPTX2 was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating NPTX2 methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, p = 0.0067). Dynamics of circulating NPTX2 methylation levels correlated with disease progression and response to therapy and predicted better than CA19-9 the evolution of disease in mPDAC patients. Remarkably, in many cases the disease progression detected by CT scan was anticipated by an increase in circulating NPTX2 methylation levels.</p><p><strong>Conclusions: </strong>Our study supports circulating NPTX2 methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"118"},"PeriodicalIF":5.7,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Quantification of hematopoietic stem and progenitor cells by targeted DNA methylation analysis.","authors":"Ledio Bocova,&nbsp;Wouter Hubens,&nbsp;Cordula Engel,&nbsp;Steffen Koschmieder,&nbsp;Edgar Jost,&nbsp;Wolfgang Wagner","doi":"10.1186/s13148-023-01532-7","DOIUrl":"https://doi.org/10.1186/s13148-023-01532-7","url":null,"abstract":"","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"117"},"PeriodicalIF":5.7,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal DNA methylation within genes of the steroidogenesis pathway two years after paediatric critical illness and association with stunted growth in height further in time.","authors":"Ilse Vanhorebeek,&nbsp;Grégoire Coppens,&nbsp;Fabian Güiza,&nbsp;Inge Derese,&nbsp;Pieter J Wouters,&nbsp;Koen F Joosten,&nbsp;Sascha C Verbruggen,&nbsp;Greet Van den Berghe","doi":"10.1186/s13148-023-01530-9","DOIUrl":"https://doi.org/10.1186/s13148-023-01530-9","url":null,"abstract":"<p><strong>Background: </strong>Former critically ill children show an epigenetic age deceleration 2 years after paediatric intensive care unit (PICU) admission as compared with normally developing healthy children, with stunted growth in height 2 years further in time as physical correlate. This was particularly pronounced in children who were 6 years or older at the time of critical illness. As this age roughly corresponds to the onset of adrenarche and further pubertal development, a relation with altered activation of endocrine pathways is plausible. We hypothesised that children who have been admitted to the PICU, sex- and age-dependently show long-term abnormal DNA methylation within genes involved in steroid hormone synthesis or steroid sulphation/desulphation, possibly aggravated by in-PICU glucocorticoid treatment, which may contribute to stunted growth in height further in time after critical illness.</p><p><strong>Results: </strong>In this preplanned secondary analysis of the multicentre PEPaNIC-RCT and its follow-up, we compared the methylation status of genes involved in the biosynthesis of steroid hormones (aldosterone, cortisol and sex hormones) and steroid sulphation/desulphation in buccal mucosa DNA (Infinium HumanMethylation EPIC BeadChip) from former PICU patients at 2-year follow-up (n = 818) and healthy children with comparable sex and age (n = 392). Adjusting for technical variation and baseline risk factors and corrected for multiple testing (false discovery rate < 0.05), former PICU patients showed abnormal DNA methylation of 23 CpG sites (within CYP11A1, POR, CYB5A, HSD17B1, HSD17B2, HSD17B3, HSD17B6, HSD17B10, HSD17B12, CYP19A1, CYP21A2, and CYP11B2) and 4 DNA regions (within HSD17B2, HSD17B8, and HSD17B10) that were mostly hypomethylated. These abnormalities were partially sex- (1 CpG site) or age-dependent (7 CpG sites) and affected by glucocorticoid treatment (3 CpG sites). Finally, multivariable linear models identified robust associations of abnormal methylation of steroidogenic genes with shorter height further in time, at 4-year follow-up.</p><p><strong>Conclusions: </strong>Children who have been critically ill show abnormal methylation within steroidogenic genes 2 years after PICU admission, which explained part of the stunted growth in height at 4-year follow-up. The abnormalities in DNA methylation may point to a long-term disturbance in the balance between active sex steroids and mineralocorticoids/glucocorticoids after paediatric critical illness, which requires further investigation.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"116"},"PeriodicalIF":5.7,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of immune cell composition with the risk factors and incidence of acute coronary syndrome.","authors":"Xian Shi,&nbsp;Minghan Qu,&nbsp;Yi Jiang,&nbsp;Ziwei Zhu,&nbsp;Chengguqiu Dai,&nbsp;Minghui Jiang,&nbsp;Lin Ding,&nbsp;Yu Yan,&nbsp;Chaolong Wang,&nbsp;Xiaomin Zhang,&nbsp;Shanshan Cheng,&nbsp;Xingjie Hao","doi":"10.1186/s13148-023-01527-4","DOIUrl":"https://doi.org/10.1186/s13148-023-01527-4","url":null,"abstract":"<p><strong>Background: </strong>Although immune cells are involved in acute coronary syndrome (ACS), few studies have explored the association of incident ACS with the relative immune cell proportions. We aimed to investigate the association of immune cell proportions with the incidence and risk factors of ACS in the Dongfeng-Tongji cohort.</p><p><strong>Methods: </strong>We conducted the analyses with 38,295 subjects from the first follow-up of the Dongfeng-Tongji cohort, including DNA methylation profiles for 1570 individuals. The proportions of immune cell types were observed from routine blood tests or estimated from DNA methylation profiles. For both observed and estimated immune cell proportions, we tested their associations with risk factors of ACS by multivariable linear regression models. In addition, the association of each immune cell proportion with incident ACS was assessed by the Cox regression model and conditional logistic regression model, respectively, adjusting for the risk factors of ACS.</p><p><strong>Findings: </strong>The proportions of lymphocytes, monocytes, and neutrophils showed strong associations with sex, followed by diabetes. Moreover, sex and current smoking were the two factors with strongest association with the proportions of lymphocyte subtypes. The hazard ratio (HR) and 95% confidence interval (CI) of incident ACS per standard deviation (SD) increase in proportions of lymphocytes and neutrophils were 0.91 (0.85-0.96) and 1.10 (1.03-1.16), respectively. Furthermore, the OR (95% CI) of incident ACS per SD increase in proportions of NK cells, CD4⁺ T cells, and B cells were 0.88 (0.78-0.99), 1.15 (1.03-1.30), and 1.13 (1.00-1.26), respectively.</p><p><strong>Interpretation: </strong>The proportions of immune cells were associated with several risk factors of ACS, including sex, diabetes, and current smoking. In addition, proportion of neutrophils had a risk effect, while proportion of lymphocytes had a protective effect on the incidence of ACS. The protective effect of lymphocytes was probably driven by NK cells.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"115"},"PeriodicalIF":5.7,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability selection enhances feature selection and enables accurate prediction of gestational age using only five DNA methylation sites.","authors":"Kristine L Haftorn, Julia Romanowska, Yunsung Lee, Christian M Page, Per M Magnus, Siri E Håberg, Jon Bohlin, Astanand Jugessur, William R P Denault","doi":"10.1186/s13148-023-01528-3","DOIUrl":"10.1186/s13148-023-01528-3","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation (DNAm) is robustly associated with chronological age in children and adults, and gestational age (GA) in newborns. This property has enabled the development of several epigenetic clocks that can accurately predict chronological age and GA. However, the lack of overlap in predictive CpGs across different epigenetic clocks remains elusive. Our main aim was therefore to identify and characterize CpGs that are stably predictive of GA.</p><p><strong>Results: </strong>We applied a statistical approach called 'stability selection' to DNAm data from 2138 newborns in the Norwegian Mother, Father, and Child Cohort study. Stability selection combines subsampling with variable selection to restrict the number of false discoveries in the set of selected variables. Twenty-four CpGs were identified as being stably predictive of GA. Intriguingly, only up to 10% of the CpGs in previous GA clocks were found to be stably selected. Based on these results, we used generalized additive model regression to develop a new GA clock consisting of only five CpGs, which showed a similar predictive performance as previous GA clocks (R² = 0.674, median absolute deviation = 4.4 days). These CpGs were in or near genes and regulatory regions involved in immune responses, metabolism, and developmental processes. Furthermore, accounting for nonlinear associations improved prediction performance in preterm newborns.</p><p><strong>Conclusion: </strong>We present a methodological framework for feature selection that is broadly applicable to any trait that can be predicted from DNAm data. We demonstrate its utility by identifying CpGs that are highly predictive of GA and present a new and highly performant GA clock based on only five CpGs that is more amenable to a clinical setting.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"114"},"PeriodicalIF":5.7,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of FDA-approved IDH inhibitors in the treatment of IDH mutated acute myeloid leukemia: a systematic review and meta-analysis.","authors":"Xiu Chen, Hongyun Xing, Xiaolu Xie, Liqiu Kou, Jun Li, Yaling Li","doi":"10.1186/s13148-023-01529-2","DOIUrl":"10.1186/s13148-023-01529-2","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).</p><p><strong>Methods: </strong>We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022.</p><p><strong>Results: </strong>A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events.</p><p><strong>Conclusion: </strong>IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":"15 1","pages":"113"},"PeriodicalIF":5.7,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}