Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes.
Poor prognosis of hepatocellular carcinoma (HCC) associated with late diagnosis necessitates the development of early diagnostic biomarkers. We have previously delineated the landscape of DNA methylation in HCC patients unraveling the importance of promoter hypomethylation in activation of cancer- a...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4ebfda4443a54d268ec3e4fa2c648e54 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4ebfda4443a54d268ec3e4fa2c648e54 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4ebfda4443a54d268ec3e4fa2c648e542021-11-18T09:00:51ZDiscovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes.1932-620310.1371/journal.pone.0068439https://doaj.org/article/4ebfda4443a54d268ec3e4fa2c648e542013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23950870/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Poor prognosis of hepatocellular carcinoma (HCC) associated with late diagnosis necessitates the development of early diagnostic biomarkers. We have previously delineated the landscape of DNA methylation in HCC patients unraveling the importance of promoter hypomethylation in activation of cancer- and metastasis-driving genes. The purpose of the present study was to test the feasibility that genes that are hypomethylated in HCC could serve as candidate diagnostic markers. We use high resolution melting analysis (HRM) as a simple translatable PCR-based method to define methylation states in clinical samples. We tested seven regions selected from the shortlist of genes hypomethylated in HCC and showed that HRM analysis of several of them distinguishes methylation states in liver cancer specimens from normal adjacent liver and chronic hepatitis in the Shanghai area. Such regions were identified within promoters of neuronal membrane glycoprotein M6-B (GPM6B) and melanoma antigen family A12 (MAGEA12) genes. Differences in HRM in the immunoglobulin superfamily Fc receptor (FCRL1) separated invasive tumors from less invasive HCC. The identified biomarkers differentiated HCC from chronic hepatitis in another set of samples from Dhaka. Although the main thrust in DNA methylation diagnostics in cancer is on hypermethylated genes, our study for the first time illustrates the potential use of hypomethylated genes as markers for solid tumors. After further validation in a larger cohort, the identified DNA hypomethylated regions can become important candidate biomarkers for liver cancer diagnosis and prognosis, especially in populations with high risk for HCC development.Barbara StefanskaAurelie BouzelmatJian HuangMatthew SudermanMichael HallettZe-Guang HanMamun Al-MahtabSheikh Mohammad Fazle AkbarWasif Ali KhanRubhana RaqibMoshe SzyfPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e68439 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Barbara Stefanska Aurelie Bouzelmat Jian Huang Matthew Suderman Michael Hallett Ze-Guang Han Mamun Al-Mahtab Sheikh Mohammad Fazle Akbar Wasif Ali Khan Rubhana Raqib Moshe Szyf Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. |
| description |
Poor prognosis of hepatocellular carcinoma (HCC) associated with late diagnosis necessitates the development of early diagnostic biomarkers. We have previously delineated the landscape of DNA methylation in HCC patients unraveling the importance of promoter hypomethylation in activation of cancer- and metastasis-driving genes. The purpose of the present study was to test the feasibility that genes that are hypomethylated in HCC could serve as candidate diagnostic markers. We use high resolution melting analysis (HRM) as a simple translatable PCR-based method to define methylation states in clinical samples. We tested seven regions selected from the shortlist of genes hypomethylated in HCC and showed that HRM analysis of several of them distinguishes methylation states in liver cancer specimens from normal adjacent liver and chronic hepatitis in the Shanghai area. Such regions were identified within promoters of neuronal membrane glycoprotein M6-B (GPM6B) and melanoma antigen family A12 (MAGEA12) genes. Differences in HRM in the immunoglobulin superfamily Fc receptor (FCRL1) separated invasive tumors from less invasive HCC. The identified biomarkers differentiated HCC from chronic hepatitis in another set of samples from Dhaka. Although the main thrust in DNA methylation diagnostics in cancer is on hypermethylated genes, our study for the first time illustrates the potential use of hypomethylated genes as markers for solid tumors. After further validation in a larger cohort, the identified DNA hypomethylated regions can become important candidate biomarkers for liver cancer diagnosis and prognosis, especially in populations with high risk for HCC development. |
| format |
article |
| author |
Barbara Stefanska Aurelie Bouzelmat Jian Huang Matthew Suderman Michael Hallett Ze-Guang Han Mamun Al-Mahtab Sheikh Mohammad Fazle Akbar Wasif Ali Khan Rubhana Raqib Moshe Szyf |
| author_facet |
Barbara Stefanska Aurelie Bouzelmat Jian Huang Matthew Suderman Michael Hallett Ze-Guang Han Mamun Al-Mahtab Sheikh Mohammad Fazle Akbar Wasif Ali Khan Rubhana Raqib Moshe Szyf |
| author_sort |
Barbara Stefanska |
| title |
Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. |
| title_short |
Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. |
| title_full |
Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. |
| title_fullStr |
Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. |
| title_full_unstemmed |
Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. |
| title_sort |
discovery and validation of dna hypomethylation biomarkers for liver cancer using hrm-specific probes. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/4ebfda4443a54d268ec3e4fa2c648e54 |
| work_keys_str_mv |
AT barbarastefanska discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT aureliebouzelmat discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT jianhuang discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT matthewsuderman discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT michaelhallett discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT zeguanghan discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT mamunalmahtab discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT sheikhmohammadfazleakbar discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT wasifalikhan discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT rubhanaraqib discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes AT mosheszyf discoveryandvalidationofdnahypomethylationbiomarkersforlivercancerusinghrmspecificprobes |
| _version_ |
1718421019893432320 |