title: Whole blood transcriptome correlates with treatment response in nasopharyngeal carcinoma.
abstract: BACKGROUND
  Treatment protocols for nasopharyngeal carcinoma (NPC) developed in the past decade have significantly improved patient survival. In most NPC patients, however, the disease is diagnosed at late stages, and for some patients treatment response is less than optimal. This investigation has two aims: to identify a blood-based gene-expression signature that differentiates NPC from other medical conditions and from controls and to identify a biomarker signature that correlates with NPC treatment response.
  
  
  METHODS
  RNA was isolated from peripheral whole blood samples (2 x 10 ml) collected from NPC patients/controls (EDTA vacutainer). Gene expression patterns from 99 samples (66 NPC; 33 controls) were assessed using the Affymetrix array. We also collected expression data from 447 patients with other cancers (201 patients) and non-cancer conditions (246 patients). Multivariate logistic regression analysis was used to obtain biomarker signatures differentiating NPC samples from controls and other diseases. Differences were also analysed within a subset (n=28) of a pre-intervention case cohort of patients whom we followed post-treatment.
  
  
  RESULTS
  A blood-based gene expression signature composed of three genes - LDLRAP1, PHF20, and LUC7L3 - is able to differentiate NPC from various other diseases and from unaffected controls with significant accuracy (area under the receiver operating characteristic curve of over 0.90). By subdividing our NPC cohort according to the degree of patient response to treatment we have been able to identify a blood gene signature that may be able to guide the selection of treatment.
  
  
  CONCLUSIONS
  We have identified a blood-based gene signature that accurately distinguished NPC patients from controls and from patients with other diseases. The genes in the signature, LDLRAP1, PHF20, and LUC7L3, are known to be involved in carcinoma of the head and neck, tumour-associated antigens, and/or cellular signalling. We have also identified blood-based biomarkers that are (potentially) able to predict those patients who are more likely to respond to treatment for NPC. These findings have significant clinical implications for optimizing NPC therapy.
authors.affiliation: Mount Miriam Cancer Hospital, 23, Jalan Bulan, Fettes Park, Tanjong Bungah 11200Penang, Malaysia.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Zaatar
authors.forename: Chun Ren
authors.initials: CR
authors.lastname: Lim
authors.forename: Chin Wei
authors.initials: CW
authors.lastname: Bong
authors.forename: Michelle Mei Lin
authors.initials: MM
authors.lastname: Lee
authors.forename: Jian Jiek
authors.initials: JJ
authors.lastname: Ooi
authors.forename: David
authors.initials: D
authors.lastname: Suria
authors.forename: Rakesh
authors.initials: R
authors.lastname: Raman
authors.forename: Samuel
authors.initials: S
authors.lastname: Chao
authors.forename: Hengxuan
authors.initials: H
authors.lastname: Yang
authors.forename: Soon Bin
authors.initials: SB
authors.lastname: Neoh
authors.forename: Choong-Chin
authors.initials: CC
authors.lastname: Liew
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000097:blood; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002277:Carcinoma; D004268:DNA-Binding Proteins; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins / Q000097:blood; D014157:Transcription Factors; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C469745:LDLRAP1 protein, human; C404083:LUC7L3 protein, human; D009687:Nuclear Proteins; C440091:PHF20 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors