title: Rsf-1 expression in rectal cancer: with special emphasis on the independent prognostic value after neoadjuvant chemoradiation.
abstract: OBJECTIVE
  Neoadjuvant chemoradiation therapy (CRT) is an increasingly used therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcome after CRT. Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness and predicts therapeutic response in certain carcinomas. However, the expression of Rsf-1 has never been reported in rectal cancer. This study examined the predictive and prognostic impacts of Rsf-1 expression in patients with rectal cancer following neoadjuvant CRT.
  
  
  METHODS
  Rsf-1 immunoexpression was retrospectively assessed for pre-treatment biopsies of 172 rectal cancer patients without initial distant metastasis. All of them were treated with neoadjuvant CRT followed by surgery. The results were correlated with the clinicopathological features, therapeutic response, tumour regression grade and metastasis-free survival (MeFS), local recurrent-free survival and disease-specific survival.
  
  
  RESULTS
  Present in 82 cases (47.7%), high-expression of Rsf-1 was associated with advanced pre-treatment tumour status (T3, T4, p=0.020), advanced post-treatment tumour status (T3, T4, p<0.001) and inferior tumour regression grade (p=0.028). Of note, high-expression of Rsf-1 emerged as an adverse prognosticator for diseases-specific survival (p=0.0092) and significantly predicted worse MeFS (p=0.0006). Moreover, high-expression of Rsf-1 also remained prognostic independent for worse MeFS (HR 2.834; p=0.0214).
  
  
  CONCLUSIONS
  High-expression of Rsf-1 is associated with poor therapeutic response and adverse outcome in rectal cancer patients treated with neoadjuvant CRT, which confers tumour aggressiveness and therapeutic resistance through chromatin remodelling and represents a potential prognostic biomarker in rectal cancer.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Ching-Yih
authors.initials: CY
authors.lastname: Lin
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Tian
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Wu
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lin
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Sheu
authors.forename: Hao-Hsien
authors.initials: HH
authors.lastname: Lee
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Yow-Ling
authors.initials: YL
authors.lastname: Shiue
authors.forename: Wen-Ren
authors.initials: WR
authors.lastname: Wu
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Hsu
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Shang-Hung
authors.initials: SH
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D059186:Chemoradiotherapy, Adjuvant; D016009:Chi-Square Distribution; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan; 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