Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women's Cancers.
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ABSTRACT:
SUBMITTER: Bartlett TE
PROVIDER: S-EPMC4667934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Differences in DNA methylation (DNAm) levels are amongst the earliest changes in human carcinogenesis, and are a hallmark of cancer, offering the potential for novel strategies to predict cancer biology and outcome. Hence, DNAm markings might provide a valuable lead for the development of DNA-based cancer biomarkers in tissue and bodily fluids. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 480,000 CpGs in a total of 221 samples, including 171 serous, 18 endometrioid, 14 clear cell, 9 mucinous and 9 other histological cancer subtypes.
2015-08-13 | GSE72021 | GEO
Project description:Differences in DNA methylation (DNAm) levels are amongst the earliest changes in human carcinogenesis, and are a hallmark of cancer, offering the potential for novel strategies to predict cancer biology and outcome. Hence, DNAm markings might provide a valuable lead for the development of DNA-based cancer biomarkers in tissue and bodily fluids. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 480,000 CpGs in a total of 221 samples, including 171 serous, 18 endometrioid, 14 clear cell, 9 mucinous and 9 other histological cancer subtypes. Bisulphite converted DNA from the 221 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip
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Project description:MicroRNA-874 (miR-874) is downregulated in several human cancers and has been suggested to be a tumor suppressor gene. However, the molecular mechanism of miR-874 downregulation in breast cancer has not been well elucidated. Here we aimed to study the aberrant hyper-methylation of CpG sites with the utility of miR-874 downreregulation in breast cancer and evaluate the clinical function of miR-874 as a prognostic marker. The miR-874 expressions in cells and tissues of two breast cancer lines were measured by real-time PCR. The DNA methylation status of the miR-874 promoter region in 19 pairs of breast cancer and adjacent normal samples was analyzed with Sequenom EpiTYPER MassArray. To evaluate whether miR-874 is a potential prognostic marker in breast cancer, we also explored the clinical long-time follow-up records from The Cancer Genome Atlas (TCGA). We found miR-874 expression was downregulated in 47 pairs of breast cancer tissues. Moreover, univariate and multivariate analysis revealed miR-874 expression may be a prognostic biomarker of overall survival in breast cancer patients. Preconditioning with 5-Aza-CdR in two cell lines elevated miR-874 expressions. The data from Sequenom EpiTYPER MassArray showed that DNA methylation of the promoter region of miR-874 was upregulated and accompanied by decreased miR-874 expression, which was further confirmed by TCGA. After comprehensive considerations, we think miR-874, which might be served as a prognostic biomarker, is mediated by DNA methylation.
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Project description:BackgroundDNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Tumor Associated Calcium Signal Transducer 2 (TACSTD2) participates in cell cycle progression through MAPK signalling pathway activation. Moreover, tumor-specific hypermethylation and association with aggressive cancer characteristics has been found for lung adenocarcinoma, hepatocellular carcinoma and cholangiocarcinoma. Whether TACSTD2 is tumor specifically hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet.MethodsQuantitative methylation-specific PCR (qMSP) analysis of a locus in the intron 1 region of TACSTD2 gene was carried out in a cross-sectional study of 127 paired RCC and normal samples. In silico analysis of TACSTD2 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset of 280 patients served as validation cohort. Statistical analyses were carried out using the two-sided paired t-test for matched tumor and normal sample comparisons, logistic regression for subgroup comparisons, Cox regression for analysis of recurrence free survival (RFS) and Pearson correlation analysis for correlation of TACSTD2 methylation and TACSTD2 mRNA in KIRC data.ResultsHigher methylation levels in RCC were significantly associated with advanced disease (p < 0.001), high tumor stage (p = 0.003), tumor differentiation (p = 0.033) and presence of lymph node (p = 0.021) or distant metastases (p = 0.008). TACSTD2 hypermethylation was associated with a shorter RFS of patients and demonstrate statistical independency from clinical parameters as state of metastasis, tumor stage, grade and state of advanced disease. In silico validation using TCGA KIRC data also demonstrated association of TACSTD2 loci with adverse clinicopathology and shortened RFS of patients. In addition, in silico analyses of TCGA KIRC data showed an inverse correlation between DNA methylation levels of TACSTD2 and mRNA expression.ConclusionsOur results suggest an association between TACSTD2 methylation and disease progression and clinical course of RCC.
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