Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas

Annette M. Lim, Nicholas C. Wong, Ruth Pidsley, Elena Zotenko, June Corry, Alexander Dobrovic, Susan J. Clark, Danny Rischin, Benjamin Solomon

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: DNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 109 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array. Data pre-processing, quality control and analysis were performed using R packages. Probes mapping to SNPs, sex chromosomes and unreliable probes were accounted for prior to downstream analyses. The relationship between methylation and patient survival was examined using both agnostic approaches and feature selection. The cohort was enlarged by incorporation of 331 The Cancer Genome Atlas (TCGA) HNSCC samples, which included 91 TCGA OTSCC samples with HM450K and survival data available. Results: Given the use of FFPE-derived DNA, we defined different cohorts for separate analyses. Overall, similar results were found between cohorts. With an unsupervised approach, no distinct hypermethylated group of samples was identified and nor was a prognostic methylation profile identified. The use of multiple downstream feature selection approaches, including a linear models for microarray data (LIMMA), centroid feature selection (CFS), and recursive feature elimination (RFE) support vector machines, similarly failed to identify a significant methylation signature informative for patient prognosis or any clinicopathological data available. Furthermore, we were unable to confirm the prognostic methylation profiles or specific prognostic loci reported within the literature for HNSCC. Conclusions: With genome-scale assessment of DNA methylation using HM450K in one of the largest OTSCC cohorts to date, we were unable to identify a hypermethylated group of tumours or a prognostic methylation signature. This suggests that either DNA methylation in isolation is not likely to be of prognostic value or larger cohorts are required to identify such a biomarker for OTSCC.

Original languageEnglish
Article number74
Number of pages12
JournalClinical Epigenetics
Volume8
Issue number1
DOIs
Publication statusPublished - 18 Jul 2016
Externally publishedYes

Keywords

  • DNA methylation
  • Epigenetics
  • HM450K
  • Oral carcinoma
  • Profiling
  • Survival
  • Tongue

Cite this

Lim, Annette M. ; Wong, Nicholas C. ; Pidsley, Ruth ; Zotenko, Elena ; Corry, June ; Dobrovic, Alexander ; Clark, Susan J. ; Rischin, Danny ; Solomon, Benjamin. / Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas. In: Clinical Epigenetics. 2016 ; Vol. 8, No. 1.
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title = "Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas",
abstract = "Background: DNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 109 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array. Data pre-processing, quality control and analysis were performed using R packages. Probes mapping to SNPs, sex chromosomes and unreliable probes were accounted for prior to downstream analyses. The relationship between methylation and patient survival was examined using both agnostic approaches and feature selection. The cohort was enlarged by incorporation of 331 The Cancer Genome Atlas (TCGA) HNSCC samples, which included 91 TCGA OTSCC samples with HM450K and survival data available. Results: Given the use of FFPE-derived DNA, we defined different cohorts for separate analyses. Overall, similar results were found between cohorts. With an unsupervised approach, no distinct hypermethylated group of samples was identified and nor was a prognostic methylation profile identified. The use of multiple downstream feature selection approaches, including a linear models for microarray data (LIMMA), centroid feature selection (CFS), and recursive feature elimination (RFE) support vector machines, similarly failed to identify a significant methylation signature informative for patient prognosis or any clinicopathological data available. Furthermore, we were unable to confirm the prognostic methylation profiles or specific prognostic loci reported within the literature for HNSCC. Conclusions: With genome-scale assessment of DNA methylation using HM450K in one of the largest OTSCC cohorts to date, we were unable to identify a hypermethylated group of tumours or a prognostic methylation signature. This suggests that either DNA methylation in isolation is not likely to be of prognostic value or larger cohorts are required to identify such a biomarker for OTSCC.",
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year = "2016",
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Lim, AM, Wong, NC, Pidsley, R, Zotenko, E, Corry, J, Dobrovic, A, Clark, SJ, Rischin, D & Solomon, B 2016, 'Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas' Clinical Epigenetics, vol. 8, no. 1, 74. https://doi.org/10.1186/s13148-016-0235-0

Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas. / Lim, Annette M.; Wong, Nicholas C.; Pidsley, Ruth; Zotenko, Elena; Corry, June; Dobrovic, Alexander; Clark, Susan J.; Rischin, Danny; Solomon, Benjamin.

In: Clinical Epigenetics, Vol. 8, No. 1, 74, 18.07.2016.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas

AU - Lim, Annette M.

AU - Wong, Nicholas C.

AU - Pidsley, Ruth

AU - Zotenko, Elena

AU - Corry, June

AU - Dobrovic, Alexander

AU - Clark, Susan J.

AU - Rischin, Danny

AU - Solomon, Benjamin

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AB - Background: DNA methylation profiling of heterogeneous head and neck squamous cell carcinoma (HNSCC) cohorts has been reported to predict patient outcome. We investigated if a prognostic DNA methylation profile could be found in tumour tissue from a single uniform subsite, the oral tongue. The methylation status of 109 comprehensively annotated oral tongue squamous cell carcinoma (OTSCC) formalin-fixed paraffin-embedded (FFPE) samples from a single institution were examined with the Illumina HumanMethylation450K (HM450K) array. Data pre-processing, quality control and analysis were performed using R packages. Probes mapping to SNPs, sex chromosomes and unreliable probes were accounted for prior to downstream analyses. The relationship between methylation and patient survival was examined using both agnostic approaches and feature selection. The cohort was enlarged by incorporation of 331 The Cancer Genome Atlas (TCGA) HNSCC samples, which included 91 TCGA OTSCC samples with HM450K and survival data available. Results: Given the use of FFPE-derived DNA, we defined different cohorts for separate analyses. Overall, similar results were found between cohorts. With an unsupervised approach, no distinct hypermethylated group of samples was identified and nor was a prognostic methylation profile identified. The use of multiple downstream feature selection approaches, including a linear models for microarray data (LIMMA), centroid feature selection (CFS), and recursive feature elimination (RFE) support vector machines, similarly failed to identify a significant methylation signature informative for patient prognosis or any clinicopathological data available. Furthermore, we were unable to confirm the prognostic methylation profiles or specific prognostic loci reported within the literature for HNSCC. Conclusions: With genome-scale assessment of DNA methylation using HM450K in one of the largest OTSCC cohorts to date, we were unable to identify a hypermethylated group of tumours or a prognostic methylation signature. This suggests that either DNA methylation in isolation is not likely to be of prognostic value or larger cohorts are required to identify such a biomarker for OTSCC.

KW - DNA methylation

KW - Epigenetics

KW - HM450K

KW - Oral carcinoma

KW - Profiling

KW - Survival

KW - Tongue

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