Prevalidation of salivary biomarkers for oral cancer detection.
BACKGROUND
Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL).


METHODS
Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL.


RESULTS
Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts.


CONCLUSIONS
The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies.


CONCLUSIONS
Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects.
School of Dentistry, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
David
D
Elashoff
Hui
H
Zhou
Jean
J
Reiss
Jianghua
J
Wang
Hua
H
Xiao
Bradley
B
Henson
Shen
S
Hu
Martha
M
Arellano
Uttam
U
Sinha
Anh
A
Le
Diana
D
Messadi
Marilene
M
Wang
Vishad
V
Nabili
Mark
M
Lingen
Darly
D
Morris
Timothy
T
Randolph
Ziding
Z
Feng
David
D
Akin
Dragana A
DA
Kastratovic
David
D
Chia
Elliot
E
Abemayor
David T W
DT
Wong
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012463:Saliva / Q000737:chemistry*
D014408:Biomarkers, Tumor; D016209:Interleukin-8; D009363:Neoplasm Proteins; D012333:RNA, Messenger