Integrated analysis of gene expression and methylation profiles of 48 candidate genes in breast cancer patients

Li, Zibo; Heng, Jianfu; Yan, Jinhua; Guo, Xinwu; Tang, Lili; Chen, Ming; Peng, Limin; Wu, Yepeng; Wang, Shouman; Zhi, Xu; Deng, Zhongping; Dai, Linjie; Wang, Jun

doi:10.1007/s10549-016-4004-8

Cited by 33 publications

(26 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AKT1 showed significant difference of expression between tumor and normal tissue in TCGA but with higher expression in tumor. The discrepancy observed here is most likely related to the differences in detection methods, stage or type of breast tumor, and even the differences in race or ethnicity [36]. …”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients

Heng

Guo

et al. 2017

PLoS ONE

Self Cite

View full text Add to dashboard Cite

BackgroundAs downstream mediators of PI3K /PTEN /AKT /mTORC1 pathway, the AKT isoforms play critical roles in tumorgenesis. Although the pleiotropic effects of AKT1 in breast cancer have been reported, the genetic and epigenetic characteristics of AKT1 promoter region in breast cancer remains to be identified. In this study we aimed to investigate the promoter mutation spectrum, methylation and gene expression pattern of AKT1 and their relationship with breast cancer.MethodsBy using PCR target sequence enrichment and next-generation sequencing technology, we sequenced AKT1 promoter region in pairs of breast tumor and normal tissues from 95 unselected Chinese breast cancer patients. The methylation of the promoter region and the expression profile of AKT1 in the same cohort were detected with bisulfite next-generation sequencing and qPCR, respectively.ResultsWe identified 28 somatic mutations in 23 of the 95 (24.2%) breast cancer samples. And 19 of the 28 mutations were located in transcription factor (TF) binding sites. In the 23 patients with somatic mutations, no significant change of methylation or expression was found comparing with other patients. AKT1 promoter region was significantly hypo-methylated in tumor compared with matched normal tissue (P = 0.0014) in the 95 patients. The expression of AKT1 was significantly suppressed in tumor tissue (P = 0.0375). In clinicopathological factor analysis, AKT1 showed significant hypo-methylation (P = 0.0249) and suppressed expression (P = 0.0375) in HER2 negative subtype. And a trend of decrease in expression level (P = 0.0624) of AKT1 in the ER negative subtype was observed, which is significantly decreased in basal-like breast tumor (P = 0.0328).ConclusionsHypo-methylation and suppressed expression of AKT1 was observed to be associated with breast cancer in our cohort. The methylation and expression of AKT1 were both significantly associated with HER2 status. The promoter mutation of AKT1 did not show significant association with its methylation and expression status. These results suggested that the promoter mutation, methylation and gene expression of AKT1 may play distinct roles in tumorgenesis of breast cancer and the integrated analysis of methylation and expression of AKT1 might serve as potential biomarkers for diagnosis and classification of breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients

Heng

Guo

et al. 2017

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to the 29 genes we studied here, 6 more telomere related genes ( CTC1, MRE11, TRF2, UPF, TIN2 , and TNKS2 ) were beyond the online software's parameters for promoter methylation primer design and were excluded from the study. The other two crucial genes TERT and WRN have been studied in our previous methylation and expression analysis [40, 41]. To our knowledge, this is the first comprehensive study of methylation on a large number (29) of telomere related genes in a relative large number of samples (184 breast cancer patients).…”

Section: Discussionmentioning

confidence: 99%

“…However lately, a more complex pattern has been reported that gene expression and methylation may be both positively and negatively correlated [41, 51]. Clinically relevant aberrant methylation may serve as a potential biomarker which is not always linked with changes in gene expression [52].…”

Section: Discussionmentioning

confidence: 99%

“…We noticed that DNA methylation was obtained from Illumina Infinium Human Methylation450 Beadchip and gene expression was obtained from RNASeq in TCGA Data Portal for breast cancer. The discrepancy observed here is most likely related to the differences in detection methods, stage or type of breast tumor, and even the differences in race or ethnicity [41]. …”

Section: Discussionmentioning

confidence: 99%

“…DNA and total RNA was extracted from fresh frozen tissue samples as previously described [40, 41]. Sodium bisulfite conversion of 500 ng genomic DNA was carried out using the EZ DNA Methylation-Lightning TM Kit (Zymo Research, Irvine, CA, USA) according to the manufacturer's instruction.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Integrated analysis of promoter methylation and expression of telomere related genes in breast cancer

et al. 2017

Self Cite

View full text Add to dashboard Cite

Telomeres at the ends of eukaryotic chromosomes play a critical role in tumorgenesis. Using microfluidic PCR and next-generation bisulfite sequencing technology, we investigated the promoter methylation of 29 telomere related genes in paired tumor and normal tissues from 184 breast cancer patients. The expression of significantly differentially methylated genes was quantified using qPCR method.We observed that the average methylation level of the 29 telomere related genes was significant higher in tumor than that in normal tissues (P = 4.30E-21). A total of 4 genes (RAD50, RTEL, TERC and TRF1) showed significant hyper-methylation in breast tumor tissues. RAD51D showed significant methylation difference among the four breast cancer subtypes. The methylation of TERC showed significant association with ER status of breast cancer. The expression profiles of the 4 hyper-methylated genes showed significantly reduced expression in tumor tissues. The integration analysis of methylation and expression of these 4 genes showed a good performance in breast cancer prediction (AUC = 0.947).Our results revealed the methylation pattern of telomere related genes in breast cancer and suggested a novel 4-gene panel might be a valuable biomarker for breast cancer diagnosis.

show abstract

Epigenetics: Strategies for Prevention Research

Karmaus

Ziyab

Mukherjee

2019

Health Impacts of Developmental Exposure to Environmental Chemicals

View full text Add to dashboard Cite

Integrated analysis of gene expression and methylation profiles of 48 candidate genes in breast cancer patients

Cited by 33 publications

References 31 publications

Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients

Integrated analysis of promoter mutation, methylation and expression of AKT1 gene in Chinese breast cancer patients

Integrated analysis of promoter methylation and expression of telomere related genes in breast cancer

Epigenetics: Strategies for Prevention Research

Contact Info

Product

Resources

About