A Multilocus Blood-Based Assay Targeting Circulating Tumor DNA Methylation Enables Early Detection and Early Relapse Prediction of Colorectal Cancer

Cai, Guoxiang; Cai, Ming‐Yan; Feng, Zhiqiang; Li, Rui; Li, Liang; Zhou, Ping‐Hong; Zhu, Boqun; Mo, Shaobo; Wang, Hui; Lan, Xiao-Liang; Cai, Sanjun; Xu, Ye; Wang, Renjie; Dai, W.; Han, Lingyu; Xiang, Wenqiang; Wang, Beili; Wei, Guo; Zhang, Lijing; Zhou, Changjiang; Luo, Bingnan; Li, Yingfei; Nie, Yuqiang; Ma, Chengcheng; Su, Zhixi

doi:10.1053/j.gastro.2021.08.054

Cited by 33 publications

(30 citation statements)

References 8 publications

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“…A recent study constructed a predictive signature of 10gene methylation in endometrial cancer (Li et al, 2021b). A group of methylation driver protein-coding genes and noncoding RNAs have been identified and experimentally confirmed in lung cancer that could be potential targets for epigenetic therapy by integrating methylation and mRNA expression profile data (Cai et al, 2021). Recently, the domestic team systematically demonstrated a multigene methylation detection method (ColonAiQ) that can realize early screening and recurrence prediction of CC, which is based on six markers for multisite blood detection (Sun et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Analysis of 5-Methylcytosine Regulators and DNA Methylation-Driven Genes in Colon Cancer

Cheng

Liu

et al. 2022

Front. Cell Dev. Biol.

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Background: Epigenetic-driven events are important molecular mechanisms of carcinogenesis. The 5-methylcytosine (5mC) regulators play important roles in the methylation-driven gene expression. However, the effect of the 5mC regulators on the oncogenic pathways in colon cancer (CC) remains unclear. Also, the clinical value of such epigenetic-driven events needs further research.Methods: The transcriptome and matching epigenetic data were obtained from The Cancer Genome Atlas dataset. The gene set variation analysis identified the oncogenic pathways adjusted by 5mC regulators. The “edgeR” and “methylmix” package identified the differential expression genes of DNA methylation-driven genes. The correlation between 5mC regulators or transcription factors and shortlisted genes was investigated by calculating the Spearman's rank correlation coefficient. Among them, the genes related to diagnosis were screened out based on differential gene expression in extracellular vesicles (EVs) by the “limma” package and histology by immunohistochemistry. Then, a risk signature was constructed by fitting the generalized linear model and validated by the receiver operating characteristic curve.Results: MYC targets pathway and phosphatidylinositol-3-kinase–AKT–mammalian target of rapamycin signaling pathway were identified as the hallmark-related pathways associated with 5mC regulators. Also, the P53 pathway was subject to the influence of regulators' expression. A five methylation-driven gene signature (FIRRE, MYBL2, TGFBI, AXIN2, and SLC35D3) was developed as the biomarker for CC diagnosis. Meanwhile, those genes positively related to 5mC regulators and interacted with their relevant or transcription factors.Conclusion: In general, 5mC regulators are positively related to each other and DNA methylation-driven genes, with the relationship of multiple active and inhibitory pathways related to cancer. Meanwhile, the signature (FIRRE, MYBL2, TGFBI, AXIN2, and SLC35D3) can prefigure prospective diagnosis in CC.

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Section: Discussionmentioning

confidence: 99%

Analysis of 5-Methylcytosine Regulators and DNA Methylation-Driven Genes in Colon Cancer

Cheng

Liu

et al. 2022

Front. Cell Dev. Biol.

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“…Sixty CRC and 20 AA tissue samples were used as case samples, and 28 healthy colon tissue samples served as control samples. 48 The number of CpGs is positively correlated with fragment size, whereas sequencing depth is negatively correlated with fragment size. To select the most informative methylation haplotypes, we only selected haplotypes with lengths ranging from 20 to 75 and greater than 3 CpGs, which balanced the information carried by the haplotype and sequence depth.…”

Section: Methodsmentioning

confidence: 99%

Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: a multicentre cohort study

Dai

Wang

et al. 2023

eClinicalMedicine

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“…Several attributes to this covalent modification landscape include regulation of transcription, accessibility of the DNA template, DNA repair signaling, etc. A fine balance maintains the normal profile of the cell and an imbalance can be associated with development of diseased states including cancer, neuronal disorder, impaired DNA repair, exposure associated disorders [6,27,42,51]. In the present issue, Dhar et al [12] and Banerjee et al [2] outlines some of the major aspects of DNA methylation and how it affects gene expression and development of neuronal disorder like autism.…”

Section: Covalent Modifications Of the Chromatin Lead To Epigenetically Regulated Expression Profilementioning

confidence: 95%

Impact of epigenetics on human health and possible tool for remediation

Paul

2021

Nucleus

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A Multilocus Blood-Based Assay Targeting Circulating Tumor DNA Methylation Enables Early Detection and Early Relapse Prediction of Colorectal Cancer

Cited by 33 publications

References 8 publications

Analysis of 5-Methylcytosine Regulators and DNA Methylation-Driven Genes in Colon Cancer

Analysis of 5-Methylcytosine Regulators and DNA Methylation-Driven Genes in Colon Cancer

Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: a multicentre cohort study

Impact of epigenetics on human health and possible tool for remediation

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