53BP1 expression is a modifier of the prognostic value of lymph node ratio and CA 19-9 in pancreatic adenocarcinoma

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.