title: Presence of CHD1L over-expression is associated with aggressive tumor biology and is a novel prognostic biomarker for patient survival in human breast cancer.
abstract: BACKGROUND
  The chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure.
  
  
  METHODS
  In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines.
  
  
  RESULTS
  Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029-4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086-7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788-15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line.
  
  
  CONCLUSIONS
  Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer.
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Pathology Department, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Fei
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Huang
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: He
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Chen
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yafen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Kunwei
authors.initials: K
authors.lastname: Shen
authors.affiliation: Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D004265:DNA Helicases; C543585:CHD1L protein, human