title: Novel biomarkers of nasopharyngeal carcinoma metastasis risk identified by reverse phase protein array based tumor profiling with consideration of plasma Epstein-Barr virus DNA load.
abstract: In patients with Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC), intertumor heterogeneity causes interpatient heterogeneity in the risk of distant metastasis. We aimed to identify novel biomarkers of metastasis risk using reverse phase protein array (RPPA) profiling of NPC patients at risk for metastasis and considering plasma EBV DNA load.
  
  
  
  A total of 98 patients with NPC with and without metastasis after treatment, matched with respect to clinical parameters, are enrolled. Total protein expression is measured by RPPA, and protein functions are analyzed by pathway bioinformatics.
  
  
  
  The RPPA analysis revealed a profile of 70 proteins that are differentially expressed in metastatic and nonmetastatic tumors. Plasma EBV DNA load after treatment correlated with protein expression level better than plasma EBV DNA load before treatment did. The biomarkers of NPC metastasis identified by proteomics regulate signaling pathways involved in cell cycle progression, apoptosis, and epithelial-mesenchymal transition. The authors identified 26 biomarkers associated with 5-year distant failure-free survival in univariate analysis; five biomarkers remained significant in multivariate analysis.
  
  
  
  A comprehensive RPPA profiling study is warranted to identify novel metastasis-related biomarkers and further examine the activation state of signaling proteins to improve estimation of metastasis risk for patients with EBV-associated NPC.
authors.affiliation: Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China.|Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R., China.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R., China.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Bojin
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, P. R., China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Medical Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sehgal
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R., China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China.
authors.forename: Guoyi
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R., China.
authors.forename: Anfei
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R., China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: Francois X
authors.initials: FX
authors.lastname: Claret
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D009362:Neoplasm Metastasis; D040081:Protein Array Analysis; D018570:Risk Assessment
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral
keywords: Biomarkers; Epstein-Barr virus (EBV); Metastasis; Nasopharyngeal carcinoma; Reverse phase protein array (RPPA)