title: Quantitative proteomic analysis for novel biomarkers of buccal squamous cell carcinoma arising in background of oral submucous fibrosis.
abstract: In 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.
  
  
  
  We 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.
  
  
  
  In 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.
  
  
  
  The 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China. liningbeta@hotmail.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Canhua
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Xinqun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Oral Medicine, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Chunjiao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Oral Medicine, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Oral Medicine, Xiangya Hospital, Central South University, No. 88, Xiangya Road, Changsha, China.
authors.forename: Changyun
authors.initials: C
authors.lastname: Fang
mesh_terms: D000328:Adult; D017314:Annexin A4 / Q000378:metabolism*; D001208:Asia; D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D064448:Filamins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009914:Oral Submucous Fibrosis / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D016019:Survival Analysis; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D017314:Annexin A4; D015415:Biomarkers; C578663:FLNA protein, human; D064448:Filamins
keywords: Annexin A4; Buccal squamous cell carcinoma; Filamin-A; Oral submucous fibrosis; Quantitative proteomic analysis