Dataset Information

Integrative Analysis of DNA Methylation and Gene Expression Identified Follicular Thyroid Cancer-Specific Diagnostic Biomarkers.

ABSTRACT: The diagnosis of follicular thyroid carcinoma (FTC) prior surgical resection remains a challenge, as routine screening methods, such as ultrasound or even FNAB, could not diagnose FTC preoperatively. Here, we performed an integrative analysis of DNA methylation and RNA array data from our own cohort (14 Follicular thyroid carcinoma vs 16 Benign thyroid lesion) to identify thyroid cancer-specific DNA methylation markers. We first identified differentially methylated and expressed genes and examined their correlations. Candidate DNA methylation sites were selected and further verified in validation set. Among all candidate methylation sites, cg06928209 was the most promising site as a molecular marker for early diagnosis, with a sensitivity of 90%, a specificity of 80% and an AUC of 0.77. Overall, our study demonstrates the potential use of methylation markers in FTC diagnosis and may boost the development of new epigenetic therapies.

SUBMITTER: Yao Y

PROVIDER: S-EPMC8964406 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Integrative Analysis of DNA Methylation and Gene Expression Identified Follicular Thyroid Cancer-Specific Diagnostic Biomarkers.

Yao Yunjin Y Xu Peiwei P Ying Tianxing T Wang Yue Y Wang Xumeng X Shu Liqi L Mo Zhe Z Chen Zhijian Z Wang Xiaofeng X Wang Weibin W Teng Lisong L Lou Xiaoming X

Frontiers in endocrinology 20220314

The diagnosis of follicular thyroid carcinoma (FTC) prior surgical resection remains a challenge, as routine screening methods, such as ultrasound or even FNAB, could not diagnose FTC preoperatively. Here, we performed an integrative analysis of DNA methylation and RNA array data from our own cohort (14 Follicular thyroid carcinoma vs 16 Benign thyroid lesion) to identify thyroid cancer-specific DNA methylation markers. We first identified differentially methylated and expressed genes and examin ...[more]

PMID: 35370931

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Project description:Background: DNA methylation is a common event in the early development of various tumors, including breast cancer (BRCA), which has been studies as potential tumor biomarkers. Although previous studies have reported a cluster of aberrant promoter methylation changes in BRCA, none of these research groups have proved the specificity of these DNA methylation changes. Here we aimed to identify specific DNA methylation signatures in BRCA which can be used as diagnostic and prognostic markers. Methods: Differentially methylated sites were identified using the Cancer Genome Atlas (TCGA) BRCA data set. We screened for BRCA-differential methylation by comparing methylation profiles of BRCA patients, healthy breast biopsies and blood samples. These differential methylated sites were compared to nine main cancer samples to identify BRCA specific methylated sites. A BayesNet model was built to distinguish BRCA patients from healthy donors. The model was validated using three Gene Expression Omnibus (GEO) independent data sets. In addition, we also carried out the Cox regression analysis to identify DNA methylation markers which are significantly related to the overall survival (OS) rate of BRCA patients and verified them in the validation cohort. Results: We identified seven differentially methylated sites (DMSs) that were highly correlated with cell cycle as potential specific diagnostic biomarkers for BRCA patients. The combination of 7 DMSs achieved ~94% sensitivity in predicting BRCA, ~95% specificity comparing healthy vs. cancer samples, and ~88% specificity in excluding other cancers. The 7 DMSs were highly correlated with cell cycle. We also identified 6 methylation sites that are highly correlated with the OS of BRCA patients and can be used to accurately predict the survival of BRCA patients (training cohort: likelihood ratio = 70.25, p = 3.633 × 10-13, area under the curve (AUC) = 0.784; validation cohort: AUC = 0.734). Stratification analysis by age, clinical stage, Tumor types, and chemotherapy retained statistical significance. Conclusion: In summary, our study demonstrated the role of methylation profiles in the diagnosis and prognosis of BRCA. This signature is superior to currently published methylation markers for diagnosis and prognosis for BRCA patients. It can be used as promising biomarkers for early diagnosis and prognosis of BRCA.

Dataset Information

Integrative Analysis of DNA Methylation and Gene Expression Identified Follicular Thyroid Cancer-Specific Diagnostic Biomarkers.

Publications

Integrative Analysis of DNA Methylation and Gene Expression Identified Follicular Thyroid Cancer-Specific Diagnostic Biomarkers.

Similar Datasets

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