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

Autor: Hui He, Yi Ma, Ningning Li, Shi-Long Lu, Ling Lu, Dohun Pyeon, Steve Quattlebaum, Liwei Gao, Derek E. Smith, Tao Xu, John I. Song, Yu Cao, Ben Milam, Sophia Bornstein, Katherine K. Green, Neil D. Gross, Matthew Whinery, Dexiang Gao, Francis Hall, Jing Xiao, Feng Jin, Minjie Wei, Elyse Handley
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Saliva
lcsh:Medicine
Epigenesis
Genetic
0302 clinical medicine
Promoter Regions
Genetic
Genetics (clinical)
DNA methylation
microRNA
Methylation
Middle Aged
3. Good health
Head and Neck Neoplasms
Area Under Curve
030220 oncology & carcinogenesis
Biomarker (medicine)
Female
Adult
lcsh:QH426-470
Biology
03 medical and health sciences
stomatognathic system
Cell Line
Tumor
Biomarkers
Tumor
otorhinolaryngologic diseases
Genetics
medicine
Humans
neoplasms
Molecular Biology
Aged
Tissue
Squamous Cell Carcinoma of Head and Neck
Research
lcsh:R
Head and neck squamous cell carcinoma
Biomarker
medicine.disease
Head and neck squamous-cell carcinoma
Human genetics
lcsh:Genetics
MicroRNAs
stomatognathic diseases
Logistic Models
030104 developmental biology
Cell culture
Cancer research
Developmental Biology
Zdroj: Clinical Epigenetics
Clinical Epigenetics, Vol 10, Iss 1, Pp 1-13 (2018)
ISSN: 1868-7083
1868-7075
DOI: 10.1186/s13148-018-0470-7
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13148-018-0470-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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