DNA methylation biomarkers for head and neck squamous cell carcinoma

Zhou, Chongchang; Ye, Meng; Ni, Shumin; Li, Qun; Ye, Dong; Li, Jinyun; Shen, Zhisen; Deng, Hongxia

doi:10.1080/15592294.2018.1465790

Cited by 63 publications

(54 citation statements)

References 55 publications

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“…The TCGA consortium identified four methylator subtypes associated with colorectal cancer, each associated with differing clinico-pathological characteristics (5). In head and neck squamous cell carcinoma (HNSCC), analysis of TCGA tumour methylation data has revealed both hyper-and hypomethylated gene sets for diagnostic purposes (6).…”

Section: Resultsmentioning

confidence: 99%

Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation & copy number variants in circulating tumour DNA

Whalley

Payne

Domingo

et al. 2020

Preprint

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Background: CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA has been challenging and has only been typically at single CpG sites. Analysis of genome wide methylation in these specimens has been limited because of the relative expense of techniques need to carry this out. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples. Methods: For all experiments, the Infinium HD assay for Methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50ng), eighteen blood derived specimens (lowest input 10ng) and six matched ctDNA input (lowest input 10ng) / fresh tumour specimens (lowest input 250ng) were processed. Downstream analysis was performed in R/Bioconductor for QC metrics and differential methylation analysis as well as copy number calls. Results: Correlation coefficients for CpG methylation at the probe level averaged R2=0.99 for blood derived samples and R2>0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared R2>0.91. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample. Conclusions: The Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to a input of 10ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA.

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Section: Resultsmentioning

confidence: 99%

Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation & copy number variants in circulating tumour DNA

Whalley

Payne

Domingo

et al. 2020

Preprint

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“…The redundant biomarkers tended to cause over-fitting of the classifier and resulted in poor generalization performance, while fewer biomarkers including incomplete or damaged information often resulted in under-fitting. Although DNAm was an important biological phenomenon in the development of many different types of cancer, there was a lack of greater insight into the physiological mechanisms of disease based solely on DNAm (Vrba et al, 2020;Zhou et al, 2018). Therefore, our multi-omics-based analysis provided a unified view for understanding the interrelationship between different molecular mechanisms and the combined effects on disease processes as well as for screening biomarkers with high sensitivity and specificity (Gao et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Identification of DNA methylation patterns and biomarkers for clear-cell renal cell carcinoma by multi-omics data analysis

Liu

Tian

2020

PeerJ

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Background Tumorigenesis is highly heterogeneous, and using clinicopathological signatures only is not enough to effectively distinguish clear cell renal cell carcinoma (ccRCC) and improve risk stratification of patients. DNA methylation (DNAm) with the stability and reversibility often occurs in the early stage of tumorigenesis. Disorders of transcription and metabolism are also an important molecular mechanisms of tumorigenesis. Therefore, it is necessary to identify effective biomarkers involved in tumorigenesis through multi-omics analysis, and these biomarkers also provide new potential therapeutic targets. Method The discovery stage involved 160 pairs of ccRCC and matched normal tissues for investigation of DNAm and biomarkers as well as 318 cases of ccRCC including clinical signatures. Correlation analysis of epigenetic, transcriptomic and metabolomic data revealed the connection and discordance among multi-omics and the deregulated functional modules. Diagnostic or prognostic biomarkers were obtained by the correlation analysis, the Least Absolute Shrinkage and Selection Operator (LASSO) and the LASSO-Cox methods. Two classifiers were established based on random forest (RF) and LASSO-Cox algorithms in training datasets. Seven independent datasets were used to evaluate robustness and universality. The molecular biological function of biomarkers were investigated using DAVID and GeneMANIA. Results Based on multi-omics analysis, the epigenetic measurements uniquely identified DNAm dysregulation of cellular mechanisms resulting in transcriptomic alterations, including cell proliferation, immune response and inflammation. Combination of the gene co-expression network and metabolic network identified 134 CpG sites (CpGs) as potential biomarkers. Based on the LASSO and RF algorithms, five CpGs were obtained to build a diagnostic classifierwith better classification performance (AUC > 99%). A eight-CpG-based prognostic classifier was obtained to improve risk stratification (hazard ratio (HR) > 4; log-rank test, p-value < 0.01). Based on independent datasets and seven additional cancers, the diagnostic and prognostic classifiers also had better robustness and stability. The molecular biological function of genes with abnormal methylation were significantly associated with glycolysis/gluconeogenesis and signal transduction. Conclusion The present study provides a comprehensive analysis of ccRCC using multi-omics data. These findings indicated that multi-omics analysis could identify some novel epigenetic factors, which were the most important causes of advanced cancer and poor clinical prognosis. Diagnostic and prognostic biomarkers were identified, which provided a promising avenue to develop effective therapies for ccRCC.

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“…Subsequently, a number of studies have indicated that increased FAM135B expression can enhance the malignant phenotype of ESCC, reflected by the promotion of cell proliferation, metastasis and invasion. Furthermore, high FAM135B expression may be associated with endogenous phosphoglyceraldehyde dehydrogenase (28,41). This suggests that FAM135B is closely associated with the occurrence and development of ESCC.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, the FAM135B gene is located in human chromosome 8q24.23 (27). A number of studies have demonstrated that the FAM135B gene is associated with the occurrence and development of tumor, and can promote the proliferation, migration and invasion of tumor cells (11,14,28).…”

Section: Introductionmentioning

confidence: 99%

Expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelium to esophageal cancer: Their differences and clinical significance

Wang

Jiang

et al. 2020

Oncol Lett

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A Disintegrin And Metalloprotease Domain 29 (ADAM29) and Family with sequence similarity 135 member B (FAM135B) genes have been reported to be associated with a carcinogenic risk of esophageal squamous cell carcinoma (ESCC). However, to the best of our knowledge, the expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelial cells to ESCC has not yet been investigated. The present study aimed to investigate the expression of ADAM29 and FAM135B in normal esophageal mucosal epithelium, low-grade and high-grade esophageal intraepithelial neoplasia, and ESCC. Furthermore, the present study aimed to investigate the role of ADAM29 and FAM135B in the development of esophageal lesions. Immunohistochemistry was performed in order to detect the expression levels of ADAM29 and FAM135B proteins in normal esophageal mucosa samples (40 cases), low-grade intraepithelial neoplasia samples (20 cases), high-grade intraepithelial neoplasia samples (20 cases) and ESCC samples (40 cases). The results of the present study demonstrated that the positive rates of ADAM29 and FAM135B proteins increased gradually from normal esophageal mucosal epithelium and esophageal intraepithelial neoplasia, to ESCC (P<0.05). Furthermore, the expression levels of ADAM29 and FAM135B proteins in ESCC were not associated with age and the tumor size (P>0.05); however, the protein levels were associated with the pathological stage, clinical stage and lymph node metastasis of ESCC (P<0.05). In addition, there was a significant association between the expression levels of ADAM29 protein and FAM135B protein (χ 2 =60.071; P<0.001). The results of the present study demonstrated that the expression levels of ADAM29 and FAM135B were associated with the tumor behavior characteristics and the progression of esophageal cancer, the expression of which could be used for the diagnosis of early esophageal cancer, and provide the basis for guiding individualized treatment.

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DNA methylation biomarkers for head and neck squamous cell carcinoma

Cited by 63 publications

References 55 publications

Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation & copy number variants in circulating tumour DNA

Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation & copy number variants in circulating tumour DNA

Identification of DNA methylation patterns and biomarkers for clear-cell renal cell carcinoma by multi-omics data analysis

Expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelium to esophageal cancer: Their differences and clinical significance

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