Abstract
IntroductionEarly diagnosis of Oral Squamous Cell Carcinoma (OSCC) increases the survival rate of oral cancer. For early diagnosis, molecular biomarkers contained in samples collected non-invasively and directly from at-risk oral premalignant lesions (OPMLs) would be ideal.MethodsIn this pilot study we evaluated the potential of a novel method using commercial PerioPaper absorbent strips for non-invasive collection of oral lesion exudate material coupled with mass spectrometry-based proteomics for oral cancer biomarker discovery.ResultsOur evaluation focused on three core issues. First, using an "on-strip" processing method, we found that protein can be isolated from exudate samples in amounts compatible with large-scale mass spectrometry-based proteomic analysis. Second, we found that the OPML exudate proteome was distinct from that of whole saliva, while being similar to the OPML epithelial cell proteome, demonstrating the fidelity of our exudate collection method. Third, in a proof-of-principle study, we identified numerous, inflammation-associated proteins showing an expected increase in abundance in OPML exudates compared to healthy oral tissue exudates. These results demonstrate the feasibility of identifying differentially abundant proteins from exudate samples, which is essential for biomarker discovery studies.ConclusionsCollectively, our findings demonstrate that our exudate collection method coupled with mass spectrometry-based proteomics has great potential for transforming OSCC biomarker discovery and clinical diagnostics assay development.
Highlights
Diagnosis of Oral Squamous Cell Carcinoma (OSCC) increases the survival rate of oral cancer
Our objective was to determine whether exudate collection from oral lesions coupled with mass spectrometry (MS)-based shotgun proteomics is a viable option for oral cancer biomarker discovery
Lesion exudates should be amenable to the full suite of proteomic analysis tools, including those aimed at identifying post-translational modifications or sequence variants [21] that may serve as powerful biomarkers of oral cancer
Summary
Diagnosis of Oral Squamous Cell Carcinoma (OSCC) increases the survival rate of oral cancer. Oral cancer occurs most commonly (~90%) in the form of oral squamous cell carcinoma (OSCC) and develops in stages starting with healthy oral epithelium progressing to an Oral Pre-Malignant Lesion (OPML) and on to OSCC. The gold standard for classifying lesions is to use an incisional biopsy coupled with histological analysis [2,3]. Biopsies have numerous limitations: being invasive clinicians are hesitant to perform them, and patients are hesitant to agree to them due to the pain and discomfort of the procedure; the following histology requires expert analysis and is expensive; and issues such as undersampling can lead to misdiagnosis [4]
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