DNA methylation markers for diagnosis and prognosis of common cancers.
Xiaoke Hao,Huiyan Luo,Michal Krawczyk,Wei Wei,Wei Wei,Wenqiu Wang,Juan Wang,Ken Flagg,Jiayi Hou,Heng Zhang,Shaohua Yi,Maryam Jafari,Danni Lin,Christopher Chung,Bennett A. Caughey,Gen Li,Debanjan Dhar,William Shi,Lianghong Zheng,Rui Hou,Jie Zhu,Liang Zhao,Xin Fu,Edward Zhang,Charlotte Zhang,Jian-Kang Zhu,Michael Karin,Rui-Hua Xu,Kang Zhang +28 more
TLDR
The utility of DNA methylation profiles for differentiating tumors and normal tissues for four common cancers found that they could differentiate cancerous tissue from normal tissue with >95% accuracy and can predict prognosis and survival.Abstract:
The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.read more
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Current and future perspectives of liquid biopsies in genomics-driven oncology.
TL;DR: The potential of liquid biopsies is highlighted by studies that show they can track the evolutionary dynamics and heterogeneity of tumours and can detect very early emergence of therapy resistance, residual disease and recurrence, but their analytical validity and clinical utility must be rigorously demonstrated before this potential can be realized.
Journal ArticleDOI
Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma
Rui-Hua Xu,Wei Wei,Wei Wei,Michal Krawczyk,Wenqiu Wang,Huiyan Luo,Huiyan Luo,Ken Flagg,Shaohua Yi,William Shi,Qingli Quan,Kang Li,Lianghong Zheng,Heng Zhang,Bennett A. Caughey,Qi Zhao,Jiayi Hou,Runze Zhang,Yanxin Xu,Huimin Cai,Gen Li,Rui Hou,Zheng Zhong,Danni Lin,Xin Fu,Jie Zhu,Yaou Duan,Meixing Yu,Binwu Ying,Wengeng Zhang,Juan Wang,Edward Zhang,Charlotte Zhang,Oulan Li,Rongping Guo,Hannah Carter,Jian-Kang Zhu,Xiaoke Hao,Kang Zhang,Kang Zhang,Kang Zhang +40 more
TL;DR: This work identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated.
Journal ArticleDOI
Liquid biopsy enters the clinic - implementation issues and future challenges.
TL;DR: In this article, the authors discuss key issues and gaps in technology, clinical trial methodologies and logistics for the eventual integration of liquid biopsy into the clinical workflow, and discuss the potential applications of this technology in cancer screening and diagnosis.
Journal ArticleDOI
METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma
Ting Li,Pei Shan Hu,Zhixiang Zuo,Jin Fei Lin,Xingyang Li,Qi Nian Wu,Zhan Hong Chen,Zhao Lei Zeng,Feng Wang,Jian Zheng,Demeng Chen,Bo Li,Tie Bang Kang,Dan Xie,Dongxin Lin,Dongxin Lin,Huai-Qiang Ju,Rui-Hua Xu +17 more
TL;DR: This study revealed that METTL3, acting as an oncogene, maintained SOX2 expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in CRC.
Journal ArticleDOI
Principles of DNA methylation and their implications for biology and medicine.
Yuval Dor,Howard Cedar +1 more
TL;DR: Taking advantage of tissue-specific differences, methylation can be used to detect cell death and thereby monitor many common diseases with a simple cell-free circulating-DNA blood test.
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