Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma

Yu Cao, Katherine Green, Steve Quattlebaum, Ben Milam, Ling Lu, Dexiang Gao, Hui He, Ningning Li, Liwei Gao, Francis Hall, Matthew Whinery, Elyse Handley, Yi Ma, Tao Xu, Feng Jin, Jing Xiao, Minjie Wei, Derek Smith, Sophia Bornstein, Neil Gross & 3 others Dohun Pyeon, John Song, Shi Long Lu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: To identify aberrant promoter methylation of genomic loci encoding microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates was initially screened using HNSCC and control cell lines and further selected using HNSCC and control tissues by quantitative methylation-specific PCR (qMS-PCR). We then examined a panel of seven mgmiRs for validation in an expanded cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre-treatment HNSCC patients and 108 non-HNSCC controls was also examined using this panel of seven mgmiRs to assess the potentials of clinical utilization. Results: Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e., mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and mgmiR148a, were further found to significantly increase in HNSCC tumor tissues compared to control tissues. Using multivariable logistic regression with dichotomized variables, a combination of the seven mgmiRs had sensitivity and specificity of 92.6 and 92.4% in tissues and 76.7 and 86.1% in saliva, respectively. Area under the receiver operating curve for this panel was 0.97 in tissue and 0.93 in saliva. This model was validated by independent bootstrap validation and random forest analysis. Conclusions: mgmiR biomarkers represent a novel and promising screening tool, and the seven-mgmiR panel is able to robustly detect HNSCC in both patient tissue and saliva.

Original languageEnglish (US)
Article number43
JournalClinical Epigenetics
Volume10
Issue number1
DOIs
StatePublished - Apr 3 2018

Fingerprint

MicroRNAs
Saliva
Biomarkers
Methylation
Cell Line
Squamous Cell Carcinoma
Neck
Carcinoma, squamous cell of head and neck
Genetic Promoter Regions
Logistic Models
Sensitivity and Specificity
Polymerase Chain Reaction

Keywords

  • Biomarker
  • DNA methylation
  • Head and neck squamous cell carcinoma
  • MicroRNA
  • Saliva
  • Tissue

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma. / Cao, Yu; Green, Katherine; Quattlebaum, Steve; Milam, Ben; Lu, Ling; Gao, Dexiang; He, Hui; Li, Ningning; Gao, Liwei; Hall, Francis; Whinery, Matthew; Handley, Elyse; Ma, Yi; Xu, Tao; Jin, Feng; Xiao, Jing; Wei, Minjie; Smith, Derek; Bornstein, Sophia; Gross, Neil; Pyeon, Dohun; Song, John; Lu, Shi Long.

In: Clinical Epigenetics, Vol. 10, No. 1, 43, 03.04.2018.

Research output: Contribution to journalArticle

Cao, Y, Green, K, Quattlebaum, S, Milam, B, Lu, L, Gao, D, He, H, Li, N, Gao, L, Hall, F, Whinery, M, Handley, E, Ma, Y, Xu, T, Jin, F, Xiao, J, Wei, M, Smith, D, Bornstein, S, Gross, N, Pyeon, D, Song, J & Lu, SL 2018, 'Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma', Clinical Epigenetics, vol. 10, no. 1, 43. https://doi.org/10.1186/s13148-018-0470-7
Cao, Yu ; Green, Katherine ; Quattlebaum, Steve ; Milam, Ben ; Lu, Ling ; Gao, Dexiang ; He, Hui ; Li, Ningning ; Gao, Liwei ; Hall, Francis ; Whinery, Matthew ; Handley, Elyse ; Ma, Yi ; Xu, Tao ; Jin, Feng ; Xiao, Jing ; Wei, Minjie ; Smith, Derek ; Bornstein, Sophia ; Gross, Neil ; Pyeon, Dohun ; Song, John ; Lu, Shi Long. / Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma. In: Clinical Epigenetics. 2018 ; Vol. 10, No. 1.
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abstract = "Background: To identify aberrant promoter methylation of genomic loci encoding microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates was initially screened using HNSCC and control cell lines and further selected using HNSCC and control tissues by quantitative methylation-specific PCR (qMS-PCR). We then examined a panel of seven mgmiRs for validation in an expanded cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre-treatment HNSCC patients and 108 non-HNSCC controls was also examined using this panel of seven mgmiRs to assess the potentials of clinical utilization. Results: Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e., mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and mgmiR148a, were further found to significantly increase in HNSCC tumor tissues compared to control tissues. Using multivariable logistic regression with dichotomized variables, a combination of the seven mgmiRs had sensitivity and specificity of 92.6 and 92.4{\%} in tissues and 76.7 and 86.1{\%} in saliva, respectively. Area under the receiver operating curve for this panel was 0.97 in tissue and 0.93 in saliva. This model was validated by independent bootstrap validation and random forest analysis. Conclusions: mgmiR biomarkers represent a novel and promising screening tool, and the seven-mgmiR panel is able to robustly detect HNSCC in both patient tissue and saliva.",
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T1 - Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma

AU - Cao, Yu

AU - Green, Katherine

AU - Quattlebaum, Steve

AU - Milam, Ben

AU - Lu, Ling

AU - Gao, Dexiang

AU - He, Hui

AU - Li, Ningning

AU - Gao, Liwei

AU - Hall, Francis

AU - Whinery, Matthew

AU - Handley, Elyse

AU - Ma, Yi

AU - Xu, Tao

AU - Jin, Feng

AU - Xiao, Jing

AU - Wei, Minjie

AU - Smith, Derek

AU - Bornstein, Sophia

AU - Gross, Neil

AU - Pyeon, Dohun

AU - Song, John

AU - Lu, Shi Long

PY - 2018/4/3

Y1 - 2018/4/3

N2 - Background: To identify aberrant promoter methylation of genomic loci encoding microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates was initially screened using HNSCC and control cell lines and further selected using HNSCC and control tissues by quantitative methylation-specific PCR (qMS-PCR). We then examined a panel of seven mgmiRs for validation in an expanded cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre-treatment HNSCC patients and 108 non-HNSCC controls was also examined using this panel of seven mgmiRs to assess the potentials of clinical utilization. Results: Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e., mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and mgmiR148a, were further found to significantly increase in HNSCC tumor tissues compared to control tissues. Using multivariable logistic regression with dichotomized variables, a combination of the seven mgmiRs had sensitivity and specificity of 92.6 and 92.4% in tissues and 76.7 and 86.1% in saliva, respectively. Area under the receiver operating curve for this panel was 0.97 in tissue and 0.93 in saliva. This model was validated by independent bootstrap validation and random forest analysis. Conclusions: mgmiR biomarkers represent a novel and promising screening tool, and the seven-mgmiR panel is able to robustly detect HNSCC in both patient tissue and saliva.

AB - Background: To identify aberrant promoter methylation of genomic loci encoding microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates was initially screened using HNSCC and control cell lines and further selected using HNSCC and control tissues by quantitative methylation-specific PCR (qMS-PCR). We then examined a panel of seven mgmiRs for validation in an expanded cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre-treatment HNSCC patients and 108 non-HNSCC controls was also examined using this panel of seven mgmiRs to assess the potentials of clinical utilization. Results: Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e., mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and mgmiR148a, were further found to significantly increase in HNSCC tumor tissues compared to control tissues. Using multivariable logistic regression with dichotomized variables, a combination of the seven mgmiRs had sensitivity and specificity of 92.6 and 92.4% in tissues and 76.7 and 86.1% in saliva, respectively. Area under the receiver operating curve for this panel was 0.97 in tissue and 0.93 in saliva. This model was validated by independent bootstrap validation and random forest analysis. Conclusions: mgmiR biomarkers represent a novel and promising screening tool, and the seven-mgmiR panel is able to robustly detect HNSCC in both patient tissue and saliva.

KW - Biomarker

KW - DNA methylation

KW - Head and neck squamous cell carcinoma

KW - MicroRNA

KW - Saliva

KW - Tissue

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