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. 2011 Jan;47(1):51-5.
doi: 10.1016/j.oraloncology.2010.10.009. Epub 2010 Nov 24.

Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population

Ole Brinkmann  1 , Dragana A Kastratovic, Milovan V Dimitrijevic, Vitomir S Konstantinovic, Drago B Jelovac, Jadranka Antic, Vladimir S Nesic, Srdjan Z Markovic, Zeljko R Martinovic, David Akin, Nadine Spielmann, Hui Zhou, David T Wong
Affiliations

Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population

Ole Brinkmann et al. Oral Oncol. 2011 Jan.

Abstract

Early detection of oral squamous cell cancer (OSCC) is the key to improve the low 5-year survival rate. Using proteomic and genomic technologies we have previously discovered and validated salivary OSCC markers in American patients. The question arises whether these biomarkers are discriminatory in cohorts of different ethnic background. Six transcriptome (DUSP1, IL8, IL1B, OAZ1, SAT1, and S100P) and three proteome (IL1B, IL8, and M2BP) biomarkers were tested on 18 early and 17 late stage OSCC patients and 51 healthy controls with quantitative PCR and ELISA. Four transcriptome (IL8, IL1B, SAT1, and S100P) and all proteome biomarkers were significantly elevated (p<0.05) in OSCC patients. The combination of markers yielded an AUC of 0.86, 0.85 and 0.88 for OSCC total, T1-T2, and T3-T4, respectively. The sensitivity/specificity for OSCC total was 0.89/0.78, for T1-T2 0.67/0.96, and for T3-T4 0.82/0.84. In conclusion, seven of the nine salivary biomarkers (three proteins and four mRNAs) were validated and performed strongest in late stage cancer. Patient-based salivary diagnostics is a highly promising approach for OSCC detection. This study shows that previously discovered and validated salivary OSCC biomarkers are discriminatory and reproducible in a different ethnic cohort. These findings support the feasibility to implement multi-center, multi-ethnicity clinical trials towards the pivotal validation of salivary biomarkers for OSCC detection.

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Conflict of interest statement

Conflict of interest statement

David T. Wong is co-founder of RNAmeTRIX Inc., a molecular diagnostic company.

Figures

Figure 1
Figure 1. Protein markers and ROC curves
Salivary protein levels (mean and standard deviation) for IL1B (panel A), IL8 (panel B), M2BP (panel C); p-values with Mann-Whitney U test; “↑” indicating mean fold change between cancer and control group; panel D: ROC curve analysis for the predictive power of combined salivary biomarkers. The final logistic model included for OSCC total 3 markers (IL1B protein + SAT1 mRNA + DUSP1 mRNA), for T1-T2 3 markers (IL1B mRNA+ IL8 mRNA+ SAT1 mRNA), and for T3-T4 2 markers (IL1B protein + DUSP1 mRNA) with an AUC of 0.86, 0.85, and 0.88 respectively
Figure 2
Figure 2. mRNA markers
Salivary mRNA values (mean and standard deviation) for IL1B mRNA (panel A), IL8 (panel B), SAT1 (panel C), OAZ1 (panel D), S100P (panel E), and DUSP1 (panel F) normalized to SIR genes (GAPDH, ACTB, RPS9); p-values with Mann-Whitney U test; “↑” indicating mean fold change between cancer and control group; for IL1B mRNA, T3-T4 mean was 5.87 fold higher than T1-T2 mean
See this image and copyright information in PMC

References

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