Loss of discoidin domain receptor 1 (DDR1) via CpG methylation during EMT in epithelial ovarian cancer

Vin Yee Chung; Tuan Zea Tan; Rui Lan Huang; Hung Cheng Lai; Ruby Yun Ju Huang

doi:10.1016/j.gene.2017.09.001

Loss of discoidin domain receptor 1 (DDR1) via CpG methylation during EMT in epithelial ovarian cancer

Vin Yee Chung, Tuan Zea Tan, Rui Lan Huang, Hung Cheng Lai, Ruby Yun Ju Huang

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Epithelial ovarian cancer (EOC) can be stratified according to the stages of epithelial-mesenchymal transition (EMT). Here, we aim to identify tyrosine kinases (TKs) in EOC that correlate with the EMT subtypes. By gene expression microarray, we analyzed the expression levels of tyrosine kinases in EOC cell lines in correlation with EMT. Among the candidate TKs identified, DDR1 was expressed mainly in EOC cells with an Epithelial phenotype. Its expression was validated by qPCR, ELISA and western blotting. Using Infinium HumanMethylation27K BeadChip array and pyrosequencing, we further analyzed the CpG methylation levels at the DDR1 promoter in EOC cells and found that the CpG methylation levels of DDR1 promoter correlated negatively with the expression of DDR1 along the EMT spectrum. Therefore, EMT stratification could be a potential biomarker to predict patient response to DDR1-targeting drugs.

Original language	English
Pages (from-to)	9-15
Number of pages	7
Journal	Gene
Volume	635
DOIs	https://doi.org/10.1016/j.gene.2017.09.001
Publication status	Published - Nov 30 2017

Keywords

DDR1
DNA methylation
Epigenetics
Epithelial-mesenchymal transition
Receptor tyrosine kinase

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.gene.2017.09.001

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@article{7da93df4b725411aa9d7b2467d560ea8,

title = "Loss of discoidin domain receptor 1 (DDR1) via CpG methylation during EMT in epithelial ovarian cancer",

abstract = "Epithelial ovarian cancer (EOC) can be stratified according to the stages of epithelial-mesenchymal transition (EMT). Here, we aim to identify tyrosine kinases (TKs) in EOC that correlate with the EMT subtypes. By gene expression microarray, we analyzed the expression levels of tyrosine kinases in EOC cell lines in correlation with EMT. Among the candidate TKs identified, DDR1 was expressed mainly in EOC cells with an Epithelial phenotype. Its expression was validated by qPCR, ELISA and western blotting. Using Infinium HumanMethylation27K BeadChip array and pyrosequencing, we further analyzed the CpG methylation levels at the DDR1 promoter in EOC cells and found that the CpG methylation levels of DDR1 promoter correlated negatively with the expression of DDR1 along the EMT spectrum. Therefore, EMT stratification could be a potential biomarker to predict patient response to DDR1-targeting drugs.",

keywords = "DDR1, DNA methylation, Epigenetics, Epithelial-mesenchymal transition, Receptor tyrosine kinase",

author = "Chung, {Vin Yee} and Tan, {Tuan Zea} and Huang, {Rui Lan} and Lai, {Hung Cheng} and Huang, {Ruby Yun Ju}",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = nov,

day = "30",

doi = "10.1016/j.gene.2017.09.001",

language = "English",

volume = "635",

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T1 - Loss of discoidin domain receptor 1 (DDR1) via CpG methylation during EMT in epithelial ovarian cancer

AU - Chung, Vin Yee

AU - Tan, Tuan Zea

AU - Huang, Rui Lan

AU - Lai, Hung Cheng

AU - Huang, Ruby Yun Ju

PY - 2017/11/30

Y1 - 2017/11/30

N2 - Epithelial ovarian cancer (EOC) can be stratified according to the stages of epithelial-mesenchymal transition (EMT). Here, we aim to identify tyrosine kinases (TKs) in EOC that correlate with the EMT subtypes. By gene expression microarray, we analyzed the expression levels of tyrosine kinases in EOC cell lines in correlation with EMT. Among the candidate TKs identified, DDR1 was expressed mainly in EOC cells with an Epithelial phenotype. Its expression was validated by qPCR, ELISA and western blotting. Using Infinium HumanMethylation27K BeadChip array and pyrosequencing, we further analyzed the CpG methylation levels at the DDR1 promoter in EOC cells and found that the CpG methylation levels of DDR1 promoter correlated negatively with the expression of DDR1 along the EMT spectrum. Therefore, EMT stratification could be a potential biomarker to predict patient response to DDR1-targeting drugs.

AB - Epithelial ovarian cancer (EOC) can be stratified according to the stages of epithelial-mesenchymal transition (EMT). Here, we aim to identify tyrosine kinases (TKs) in EOC that correlate with the EMT subtypes. By gene expression microarray, we analyzed the expression levels of tyrosine kinases in EOC cell lines in correlation with EMT. Among the candidate TKs identified, DDR1 was expressed mainly in EOC cells with an Epithelial phenotype. Its expression was validated by qPCR, ELISA and western blotting. Using Infinium HumanMethylation27K BeadChip array and pyrosequencing, we further analyzed the CpG methylation levels at the DDR1 promoter in EOC cells and found that the CpG methylation levels of DDR1 promoter correlated negatively with the expression of DDR1 along the EMT spectrum. Therefore, EMT stratification could be a potential biomarker to predict patient response to DDR1-targeting drugs.

KW - DDR1

KW - DNA methylation

KW - Epigenetics

KW - Epithelial-mesenchymal transition

KW - Receptor tyrosine kinase

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DO - 10.1016/j.gene.2017.09.001

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SN - 0378-1119

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SP - 9

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JO - Gene

JF - Gene

ER -

Loss of discoidin domain receptor 1 (DDR1) via CpG methylation during EMT in epithelial ovarian cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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