单位：[1]Department of Otolaryngology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[2]Laboratory of Precision Oncology, China Medical University School of Pharmacy, No. 77 Puhe Road, Shenyang 110122, China.[3]Department of Biostatistics, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[4]Research Laboratory and Department of Hematology, Benxi Central Hospital, Benxi 117000, China.[5]Department of Medical Oncology, Peking Union Medical School Hospital, Beijing 100730, China.[6]Department of Radiation Oncology, China Japan Friendship Hospital, Beijing, China.[7]Department of Otolaryngology, The First University Hospital of China Medical University, Shenyang 110001, China.[8]Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[9]Department of Surgical Oncology, The First University Hospital of China Medical University, Shenyang 110001, China.[10]Department of Oral Pathology, Dental School of Dalian Medical University, Dalian 116044, China.[11]Department of Radiation Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.[12]Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.[13]Department of Pathology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[14]Department of Dermatology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[15]Department of Radiation Oncology, Cornell University, New York, NY, USA.[16]Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, USA.
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.
基金：
Whedon Cancer Detection Foundation; University of Colorado Cancer Center; Cancer League of Colorado; University of Colorado Academic Enrichment Fund; Dick Brown Head and Neck Research Fund; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M621178]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 DE026125]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA046934] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE026125] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Otolaryngology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[2]Laboratory of Precision Oncology, China Medical University School of Pharmacy, No. 77 Puhe Road, Shenyang 110122, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Otolaryngology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[2]Laboratory of Precision Oncology, China Medical University School of Pharmacy, No. 77 Puhe Road, Shenyang 110122, China.[13]Department of Pathology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.[14]Department of Dermatology, University of Colorado Anschutz Medical Campus, 12700 E19th Avenue, Aurora, CO 80045, USA.
推荐引用方式(GB/T 7714)：
Yu Cao,Katherine Green,Steve Quattlebaum,et al.Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma[J].CLINICAL EPIGENETICS.2018,10:doi:10.1186/s13148-018-0470-7.
APA：
Yu Cao,Katherine Green,Steve Quattlebaum,Ben Milam,Ling Lu...&Shi-Long Lu.(2018).Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma.CLINICAL EPIGENETICS,10,
MLA：
Yu Cao,et al."Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma".CLINICAL EPIGENETICS 10.(2018)
