DNA methylation markers for diagnosis and prognosis of common cancers

Kanwal Batool
SP21-RMG-008

Xiaoke Haoa,1,2, Huiyan Luob,c,1, Michal Krawczykc,1, Wei Weib,c,1, Wenqiu Wangc,d,1, Juan Wanga,1, Ken Flaggc, Jiayi
Houc, Heng Zhange, Shaohua Yic, Maryam Jafaric, Danni Linc, Christopher Chungc, Bennett A. Caugheyc, Gen Lif,
Debanjan Dharg, William Shic, Lianghong Zhengf, Rui Houf, Jie Zhuc, Liang Zhaof, Xin Fuc, Edward Zhangc, Charlotte
Zhangc, Jian-Kang Zhue, Michael Karing,2, Rui-Hua Xub,2, and Kang Zhangc,h,
 Content
• Introduction
• Objectives
• Methodology
• Results
• Conclusion
 Introduction
• Four major types of cancer were evaluated
during this study
• lung, breast, colon, and liver
• Theme of this study:
• DNA Methylation markers can be used for
prognosis of various cancers
• Hard to reach tumors
• Biopsy sample’s distorted anatomy
• Patient’s surgery tolerance level
• Quality of preserved sample
 Why methylation?
• Methylation of CpG sites epigenetic regulation of gene
expression gene silencing
• Cancer  extensive perturbations of DNA methylation 
changes in gene regulation oncogenesis
• DNA methylation analysis 95% diagnostic accuracy rate
 Objective

• To check:

• Alternative diagnostic option

• Cancer prognosis using DNA markers

 Methodology
• Complete clinical, molecular, and
histopathological datasets obtained from
TCGA and West China Hospital

• whole-genome methylation profiling 

potential cancer-specific DNA methylation
markers spotted
• DATA:
• Sample collection

• Patients
• Normal people
• Written consent
• data sources
• statistical analyses
• probe design
• oligonucleotide microarrays
• bis-DNA capture
• DNA extraction
• cell culture
• colony formation assays
• tumor xenografts
• sequencing and data analysis
• Partitioning the genome into blocks:
• Methylation-corelated blocks (MCBs)
• Comethylated CpG sites
• Survey of MCBs in normal&cancer cells
• beta values of MCBS bioinformatics tools
• Selection of top CpG markers
 Cohort Analysis
• Training Cohort  group of people 
Comparative analysis of genome

• Validation Cohort  machine based 

prediction/study model check
 Results
• Characteristics of Patients and Tissues
• Training cohort:
• 1619 tumor sample drawn
• 173 normal samples matched
• TCGA validation cohort:
• 791 tumor samples drawn from TCGA
• 93 normal sample matched
• SYU cancer center, West china hospital& Xinjing
hospital validation cohort:
• 324 normal samples MATCHED 394 tumor sample
 Cancer-Specific Methylation Signatures

• Pre-screening of data
• multiclass prediction system
• Hierarchical clustering of samples
• Correct diagnosis rate
• 98.4% for training cohort
• 97% for validation cohort
• Independent cohort 95%
Methylation markers can predict overall survival of patients in different types of cancers.
• These findings demonstrate the utility of
methylation biomarkers for the molecular
characterization of cancer, with implications
for diagnosis and prognosis.
 conclusion
• These findings support the potential for using
the DNA methylation signature to improve the
diagnosis of metastatic disease in addition to
primary cancers.

• An inverse correlation between promoter

methylation and gene expression identified
several genes known to be important in
carcinogenesis.
• These results support a functional role of
these methylation markers in promoting
carcinogenesis and provide biological
validation for their use in methylation studies
to characterize cancers.
Thank you 

Fin.