title: Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma.
abstract: OBJECTIVE
  Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC.
  
  
  METHODS
  Rsf-1 immunoexpression was retrospectively assessed in biopsies of 108 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The results were correlated with the clinicopathological features, therapeutic response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS).
  
  
  RESULTS
  Present in 49 cases (45%), Rsf-1 overexpression was associated with N(2,3) status (p=0.016), American Joint Committee on Cancer stage 3, 4 (p=0.004), and incomplete therapeutic response (p=0.041). In multivariate analyses, Rsf-1 overexpression not only emerged as the sole independent adverse prognosticator for LRFS (p=0.0002, RR 5.287) but also independently predicted worse DMFS (p=0.0011, RR 3.185) and DSS (p<0.0001, RR 4.442), along with T(3,4) (p=0.0454) and N(2,3) (p=0.0319), respectively.
  
  
  CONCLUSIONS
  Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response, which confers tumour aggressiveness through chromatin remodelling, and represents a potential prognostic biomarker in NPC.
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Tai
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Ching-Yih
authors.initials: CY
authors.lastname: Lin
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Sheu
authors.forename: Shih-Lun
authors.initials: SL
authors.lastname: Chang
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Wu
authors.forename: Yow-Ling
authors.initials: YL
authors.lastname: Shiue
authors.forename: Wen-Ren
authors.initials: WR
authors.lastname: Wu
authors.forename: Chun-Mao
authors.initials: CM
authors.lastname: Lin
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D015534:Trans-Activators / Q000032:analysis*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C452851:RSF1 protein, human; D015534:Trans-Activators