Identification of a gene signature for rapid screening of oral squamous cell carcinoma.
OBJECTIVE
Oral cancer is a major health problem worldwide and in the U.S. The 5-year survival rate for oral cancer has not improved significantly over the past 20 years and remains at approximately 50%. Patients diagnosed at an early stage of the disease typically have an 80% chance for cure and functional outcome, however, most patients are identified when the cancer is advanced. Thus, a convenient and an accurate way to detect oral cancer early will decrease patient morbidity and mortality. The ability to noninvasively monitor oral cancer onset, progression, and treatment outcomes requires two prerequisites: identification of specific biomarkers for oral cancers as well as noninvasive access to and monitoring of these biomarkers that could be conducted at the point of care (i.e., practitioner's or dentist's office) by minimally trained personnel.


METHODS
Here, we show that DNA microarray gene expression profiling of matched tumor and normal specimens can identify distinct anatomic site expression patterns and a highly significant gene signature distinguishing normal from oral squamous cell carcinoma (OSCC) tissue.


RESULTS
Using a supervised learning algorithm, we generated a 25-gene signature for OSCC that can classify normal and OSCC specimens. This 25-gene molecular predictor was 96% accurate on cross-validation, averaging 87% accuracy using three independent validation test sets and failing to predict non-oral tumors.


CONCLUSIONS
Identification and validation of this tissue-specific 25-gene molecular predictor in this report is our first step towards developing a new, noninvasive, microfluidic-based diagnostic technology for mass screening, diagnosis, and treatment of pre-OSCC and OSCC.
Ziober
Amy F
AF
Department of Otorhinolaryngology-Head and Neck Surgery, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
Patel
Kirtesh R
KR
Alawi
Faizan
F
Gimotty
Phyllis
P
Weber
Randall S
RS
Feldman
Michael M
MM
Chalian
Ara A
AA
Weinstein
Gregory S
GS
Hunt
Jennifer
J
Ziober
Barry L
BL
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008403:Mass Screening / Q000379:methods; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D012333:RNA, Messenger; D012334:RNA, Neoplasm