Abstract
BackgroundIn South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in OSF that are often not completely resected, causing local relapse. The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches.MethodsWe compared normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to discover proteins with differential expression. Gene Ontology and KEGG networks were analyzed. The prognostic value of biomarkers was evaluated in 94 BSCCs accompanied with OSF. Significant associations were assessed by Kaplan-Meier survival and Cox-proportional hazards analysis.ResultsIn total 30 proteins were identified with significantly different expression (false discovery rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4 and FLNA, were validated. The disease-free survival was negatively associated with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio, 2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs.ConclusionThe present study indicates that iTRAQ quantitative proteomics analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up-regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC prognosis but also potential targets for its therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2650-1) contains supplementary material, which is available to authorized users.
Highlights
In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF)
All patients included for both the biomarker discovery screen and the retrospective clinical validation study were diagnosed with a primary BSCC arising from OSF
The present study is the first comprehensive research on proteins with differential expression among normal buccal mucosa (NBM), OSF and BSCC arising from OSF by using the isobaric tags for relative and absolute quantification (iTRAQ) shot-gun proteomic approach [20]
Summary
In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches. Oral submucous fibrosis (OSF) is a chronic and insidious lesion of oral mucosa which demonstrates prevalent in some South and Southeast Asian countries [1, 2]. OSF is associated with raised risk for the oral squamous cell carcinoma (OSCC), especially buccal SCC (BSCC), because buccal mucosa is the most common region that is stimulated by chewing areca nut [7,8,9]. It is still hard to discover unique biomarkers to predict which oral mucosal disease will progress to OSCC [13, 14]
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