title: 53BP1 expression is a modifier of the prognostic value of lymph node ratio and CA 19-9 in pancreatic adenocarcinoma.
abstract: BACKGROUND
  53BP1 binds to the tumor suppressor p53 and has a key role in DNA damage response and repair. Low 53BP1 expression has been associated with decreased survival in breast cancer and has been shown to interact with several prognostic factors in non-small cell lung cancer. The role of 53BP1 in pancreatic ductal adenocarcinoma (PDAC) has yet to be determined. We aimed to investigate whether 53BP1 levels interact with established prognostic factors in PDAC.
  
  
  METHODS
  106 patients for whom there was tissue available at time of surgical resection for PDAC were included. A tissue microarray was constructed using surgical specimens, stained with antibodies to 53BP1, and scored for expression intensity. Univariate and multivariate statistical analyses were performed to investigate the association between 53BP1 and patient survival with known prognostic factors for survival.
  
  
  RESULTS
  The association of 53BP1 with several established prognostic factors was examined, including stage, tumor grade, surgical margin, peripancreatic extension, lymph node ratio (LNR), and CA 19-9. We found that 53BP1 modified the effects of known prognostic variables including LNR and CA 19-9 on survival outcomes. When 53BP1 intensity was low, increased LNR was associated with decreased OS (HR 4.84, 95% CI (2.26, 10.37), p<0.001) and high CA19-9 was associated with decreased OS (HR 1.72, 95% CI (1.18, 2.51), p=0.005). When 53BP1 intensity was high, LNR and CA19-9 were no longer associated with OS (p=0.958 and p=0.606, respectively).
  
  
  CONCLUSIONS
  In this study, 53BP1, a key player in DNA damage response and repair, was found to modify the prognostic value of two established prognostic factors, LNR and CA 19-9, suggesting 53BP1 may alter tumor behavior and ultimately impact how we interpret the value of other prognostic factors.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Ausborn
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Wentz
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Nipun B
authors.initials: NB
authors.lastname: Merchant
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Anuradha Bapsi
authors.initials: AB
authors.lastname: Chakravarthy
authors.forename: Fen
authors.initials: F
authors.lastname: Xia
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000556:secondary* / Q000601:surgery; D000368:Aged; D018395:CA-19-9 Antigen / Q000097:blood*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D018395:CA-19-9 Antigen; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1