Salivary transcriptome diagnostics for oral cancer detection

Yang Li, Maie A.R. St. John, Xiaofeng Zhou, Yong Kim, Uttam Sinha, Richard C.K. Jordan, David Eisele, Elliot Abemayor, David Elashoff, No Hee Park, David T. Wong

Research output: Contribution to journalArticle

Abstract

Purpose: Oral fluid (saliva) meets the demand for non-invasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease. Experimental Design: Unstimulated saliva was collected from patients (n = 32) with primary T1/T2 OSCC and normal subjects (n = 32) with matched age, gender, and smoking history. RNA isolation was done from the saliva supernatant, followed by two-round linear amplification with T7 RNA polymerase. Human Genome U133A microarrays were applied for profiling human salivary transcriptome. The different gene expression patterns were analyzed by combining a t test comparison and a fold-change analysis on 10 matched cancer patients and controls. Quantitative polymerase chain reaction (qPCR) was used to validate the selected genes that showed significant difference (P < 0.01) by microarray. The predictive power of these salivary mRNA biomarkers was analyzed by receiver operating characteristic curve and classification models. Results: Microarray analysis showed there are 1,679 genes exhibited significantly different expression level in saliva between cancer patients and controls (P < 0.05). Seven cancer-related mRNA biomarkers that exhibited at least a 3.5-fold elevation in OSCC saliva (P < 0.01) were consistently validated by qPCR on saliva samples from OSCC patients (n = 32) and controls (n = 32). These potential salivary RNA biomarkers are transcripts of ILA, IL1B, DUSP1, HA3, OAZ1, S100P, and SAT. The combinations of these biomarkers yielded sensitivity (91%) and specificity (91%) in distinguishing OSCC from the controls. Conclusions: The utility of salivary transcriptome diagnostics is successfully demonstrated in this study for oral cancer detection. This novel clinical approach could be exploited to a robust, high-throughput, and reproducible tool for early cancer detection. Salivary transcriptome profiling can be applied to evaluate its usefulness for other major disease applications as well as for normal health surveillance.

Original languageEnglish (US)
Pages (from-to)8442-8450
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number24
DOIs
StatePublished - Dec 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Li, Y., St. John, M. A. R., Zhou, X., Kim, Y., Sinha, U., Jordan, R. C. K., Eisele, D., Abemayor, E., Elashoff, D., Park, N. H., & Wong, D. T. (2004). Salivary transcriptome diagnostics for oral cancer detection. Clinical Cancer Research, 10(24), 8442-8450. https://doi.org/10.1158/1078-0432.CCR-04-1167