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Status |
Public on Feb 13, 2013 |
Title |
NID2 and HOXA9 promoter hypermethylation as biomarkers to prevent and detect Oral Cavity Squamous Cell Carcinoma |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by array
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Summary |
Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (k=0.64), HOXA9 (k=0.60), NID2 (k=0.60), and EDNRB (k=0.60) had a moderate to substantial agreement with clinical diagnosis in the Discovery screen. HOXA9 had 68% sensitivity, 100% specificity and a 0.81 AUC. NID2 had 71% sensitivity, 100% specificity and a 0.79 AUC. In the Prevalence screen HOXA9 (k=0.82) and NID2 (k=0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity and a 0.97 AUC. In saliva from OSCC cases and controls HOXA9 had 75% sensitivity, 53% specificity and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity and a 0.73 AUC. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.
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Overall design |
The 12 samples analyzed comprise equal numbers of three tissue-types: Primary oral squamous cell carcinoma, Oral leukoplakia and Normal oral mucosa. Gender, age and smoking-status were approximately equally represented in these goups. Normal oral mucosa served as a control.
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Contributor(s) |
Guerrero-Preston R, Soudry E, Acero J, Orera M, Moreno-López L, Macía-Colón G, Jaffe A, Berdasco M, Ili-Gangas C, Brebi-Mieville P, Fu Y, Engstrom C, Irizarry R, Esteller M, Westra W, Koch W, Califano J, Sidransky D |
Citation(s) |
21558411 |
Submission date |
Mar 28, 2011 |
Last update date |
Jan 02, 2015 |
Contact name |
Rafael Guerrero-Preston |
E-mail(s) |
rguerre3@jhmi.edu
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Organization name |
Johns Hopkins School of Medicine
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Street address |
1550 Orleans Street, CRBII, Rm 5M
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City |
Baltimore |
State/province |
MD |
ZIP/Postal code |
21231 |
Country |
USA |
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Platforms (1) |
GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
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Samples (12)
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GSM698565 |
M38: Normal oral mucosa |
GSM698566 |
M5: Primary oral squamous cell carcinoma tissue |
GSM698567 |
M6: Oral leukoplakia tissue |
GSM698568 |
M8: Oral leukoplakia tissue |
GSM698569 |
M9: Oral leukoplakia tissue |
GSM698570 |
M18: Primary oral squamous cell carcinoma tissue |
GSM698571 |
M35: Primary oral squamous cell carcinoma tissue |
GSM698572 |
M41: Primary oral squamous cell carcinoma tissue |
GSM698573 |
M4: Oral leukoplakia tissue |
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Relations |
BioProject |
PRJNA139669 |
Supplementary file |
Size |
Download |
File type/resource |
GSE28217_RAW.tar |
5.8 Mb |
(http)(custom) |
TAR |
GSE28217_normal_non-normalized.txt.gz |
692.7 Kb |
(ftp)(http) |
TXT |
GSE28217_oral_SCC_non-normalized.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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