title: Overexpression of Rsf-1 correlates with pathological type, p53 status and survival in primary breast cancer.
abstract: OBJECTIVE
  The incidence of breast cancer in developing countries still increasing, to identify novel molecular markers associated with carcinogenesis and prognosis of breast cancer still being implemented. The largest subunit of Remodeling and spacing factor (RSF), Rsf-1, mediates ATPase-dependent chromatin remodeling. Its oncogenic properties have been demonstrated in certain carcinomas. The aim of this study was to examine the prognostic value of Rsf-1 in patients with primary breast carcinoma.
  
  
  METHODS
  A total of 537 patients with primary breast cancer, and 54 with benign breast hyperplasia, were performed resection surgery in the same period were enrolled. Rsf-1 immunoexpression was retrospectively assessed by immunohistochemistry (IHC). As well as, it relationship with clinicopathological factors and patient survival (LRFS, DFS and OS) was investigated.
  
  
  RESULTS
  Compared with benign breast hyperplasia tissues, higher percentage of Rsf-1 positive expression was detected in malignant breast carcinomas. Based on IHC staining extent × intensity scores and ROC analysis, 278 of 526 cancers (52.9%) had high-expression (cut-off values 2.5) of Rsf-1, which correlated significantly to pathologic subtypes of breast cancer (DCIS vs. IDC, P < 0.001; ILC vs. IDC, P = 0.036), bigger tumor size (P = 0.030), higher TNM stage (P = 0.044), and p53-positive expression. In addition, there was a trend that high-expression of Rsf-1 associated with younger age (P = 0.053). We further prove that combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) was correlated with the bigger tumor size (P = 0.018), and higher TNM stage (P = 0.024). Kaplan-Meier survival analysis showed that Rsf-1 high-expression and combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) exhibited a significant correlation with poor overall survival of patients with primary breast cancer, and no association has been identified in relation to LRFS or DFS. Especially, Univariate and multivariate survival analysis demonstrated Rsf-1 expression is an independent prognostic parameter for the overall survival of patients with breast cancer.
  
  
  CONCLUSIONS
  High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling, and targeting Rsf-1 gene and the pathway it related may provide new therapeutic avenues for treating breast cancer.
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Qiu-Chen
authors.initials: QC
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, China Medical University Shenyang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Hui-Zhe
authors.initials: HZ
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Zhao-Jin
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Wei-Fan
authors.initials: WF
authors.lastname: Yao
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, Liaoning, China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Mi
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University Shenyang, Liaoning, China.
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University Shenyang, China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Wei
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016009:Chi-Square Distribution; D042002:Chromatin Assembly and Disassembly; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008408:Mastectomy; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D015534:Trans-Activators / Q000032:analysis*; D016896:Treatment Outcome; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C452851:RSF1 protein, human; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53
keywords: Rsf-1; breast cancer; chromatin remodeling; p53; prognosis