Epigenetic modifications inlysine demethylases associate with survival of early-stage NSCLC
(2018) In Clinical Epigenetics 10.- Abstract
Background: KDMlysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations inKDMgenes and their roles in lung cancer survival.
Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites inKDMgenes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate... (More)
Background: KDMlysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations inKDMgenes and their roles in lung cancer survival.
Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites inKDMgenes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation.
Results: DNA methylation at sites cg11637544 inKDM2Aand cg26662347 inKDM1Awere in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95%CI, 1.16-1.50,P = 1.1 × 10-4;HRcg26662347 = 1.88, 95%CI, 1.37-2.60,P = 3.7 × 10-3), and correlated with corresponding gene expression (cg11637544 forKDM2A,P = 1.3 × 10-10; cg26662347 forKDM1A P = 1.5 × 10-5). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance.
Conclusions: These findings highlight the association between somatic DNA methylation inKDMgenes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.
(Less)
- author
- organization
- publishing date
- 2018-04-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Journal Article
- in
- Clinical Epigenetics
- volume
- 10
- article number
- 41
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:29619118
- scopus:85044829507
- ISSN
- 1868-7075
- DOI
- 10.1186/s13148-018-0474-3
- language
- English
- LU publication?
- yes
- id
- 3e8f4be2-60aa-40da-9de1-b368b71a130c
- date added to LUP
- 2018-04-09 09:20:12
- date last changed
- 2024-09-16 19:49:54
@article{3e8f4be2-60aa-40da-9de1-b368b71a130c, abstract = {{<p>Background: KDMlysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations inKDMgenes and their roles in lung cancer survival.</p><p>Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites inKDMgenes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation.</p><p>Results: DNA methylation at sites cg11637544 inKDM2Aand cg26662347 inKDM1Awere in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95%CI, 1.16-1.50,P = 1.1 × 10-4;HRcg26662347 = 1.88, 95%CI, 1.37-2.60,P = 3.7 × 10-3), and correlated with corresponding gene expression (cg11637544 forKDM2A,P = 1.3 × 10-10; cg26662347 forKDM1A P = 1.5 × 10-5). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance.</p><p>Conclusions: These findings highlight the association between somatic DNA methylation inKDMgenes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.</p>}}, author = {{Wei, Yongyue and Liang, Junya and Zhang, Ruyang and Guo, Yichen and Shen, Sipeng and Su, Li and Lin, Xihong and Moran, Sebastian and Helland, Åslaug and Bjaanæs, Maria M and Karlsson, Anna and Planck, Maria and Esteller, Manel and Fleischer, Thomas and Staaf, Johan and Zhao, Yang and Chen, Feng and Christiani, David C}}, issn = {{1868-7075}}, keywords = {{Journal Article}}, language = {{eng}}, month = {{04}}, publisher = {{BioMed Central (BMC)}}, series = {{Clinical Epigenetics}}, title = {{Epigenetic modifications inlysine demethylases associate with survival of early-stage NSCLC}}, url = {{http://dx.doi.org/10.1186/s13148-018-0474-3}}, doi = {{10.1186/s13148-018-0474-3}}, volume = {{10}}, year = {{2018}}, }