Evaluation of Salivary Transcriptome Markers for the Early Detection of Oral Squamous Cell Cancer in a Prospective Blinded Trial.

Autor:	Martin JL; Past President, Sharpe Strumia Research Foundation, Bryn Mawr, Pennsylvania; Chief Medical Officer, PeriRx LLC, Broomall, Pennsylvania., Gottehrer N; Guest Faculty, University of Maryland Dental School, Baltimore, Maryland; Director of Dental Education, PeriRx LLC, Broomall, Pennsylvania; Diplomate, American Board of Periodontology; Private Practice, Periodontics, Havertown, Pennsylvania., Zalesin H; Attending Oral Surgeon, St. John Macomb-Oakland Hospital, Warren, Michigan., Hoff PT; Attending Physician, MI Otolaryngology Surgery Associates, Ypsilanti, Michigan., Shaw M; Director of Research, St. John Macomb-Oakland Hospital, Warren, Michigan., Clarkson JH; Assistant Professor, Michigan State University, Department of Surgery, Lansing, Michigan., Haan P; Research Coordinator, Michigan State University, Department of Surgery, Lansing, Michigan., Vartanian M; Clinical Coordinator, University of Michigan, Department of Surgery, Ann Arbor, Michigan., McLeod T; Research Nurse, Michigan State University, Department of Surgery, Lansing, Michigan., Swanick SM; Chief Executive Officer, PeriRx LLC, Broomall, Pennsylvania.
Jazyk:	angličtina
Zdroj:	Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995) [Compend Contin Educ Dent] 2015 May; Vol. 36 (5), pp. 365-73.
Abstrakt:	Background: Oral squamous cell cancer (OSCC) is often diagnosed in late stages. Informative biomarkers could play a key role in early diagnosis. Prior case-control studies identified discriminatory salivary mRNA markers for OSCC. The National Cancer Institute (NCI) recommends prospective-specimencollection, retrospective-blinded-evaluation (PRoBE) design study for rigorous biomarker identification and validation. Methods: A PRoBE design study enrolled 170 patients with lesions suspicious for OSCC. Saliva was collected before performing oral biopsy. Six pre-specified oral-cancer-associated mRNAs (IL1β, IL8, OAZ1, SAT, S100P, and DUSP1) and five housekeeping mRNAs (MT-ATP6, RPL30, RPL37A, RPL0, and RPS17) were measured by quantitative polymerase chain reaction (PCR) without knowledge of tissue diagnosis. A pre-specified multi-marker panel from prior NCI - Early Detection Research Network (EDRN) studies was evaluated in this new PRoBE dataset. Individual marker cycle thresholds (Ct) from PCR were also compared in cancer versus control, and new discriminatory models were generated. Results: The EDRN model was validated based on pre-specified statistical analysis plan. Ct values of individual mRNAs reflect an approximately twofold to nearly fourfold increase in concentration in invasive OSCC (P less than 0.01 for all). A new model from this intended-use population with incorporation of housekeeping genes demonstrates a maximal sum of sensitivity and specificity of 150.7% with an area under the receiver operating characteristic (ROC) curve of over 0.85. Conclusion: The validation of six pre-specified individual salivary transcriptome markers of OSCC and a pre-specified multi-marker model in a new prospective population supports the robustness of these markers and the multi-marker methodology. New models generated in this intended-use population have the potential to further enhance the decision process for early biopsy. Lesions at very low risk for cancer could be identified noninvasively as could those at significantly increased risk. Further study is necessary to assure effective implementation of this technology into routine clinical practice.
Databáze:	MEDLINE
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