PALB2 upregulation is associated with a poor prognosis in pancreatic ductal adenocarcinoma

PALB2 上调与胰腺导管腺癌预后不良相关

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作者:Ouyang Ge, Anle Huang, Xin Wang, Yuling Chen, Yuanchun Ye, Lutz Schomburg

Abstract

During DNA repair, BRCA1 and BRCA2 interact with the tumor suppressor partner and localizer of BRCA2 (PALB2). PALB2 mutations are associated with an increased risk of breast and ovarian carcinoma, and upregulated PALB2 expression is associated with poor clinical outcomes. The present study investigated the role and prognostic value of PALB2 in pancreatic ductal adenocarcinoma (PDAC). PALB2 expression was inhibited using a small interfering RNA in PDAC cell lines, and the subsequent effects on cell proliferation and migration were investigated. Tissue microarrays from 157 patients undergoing a pancreaticoduodenectomy for PDAC were analyzed via immunohistochemistry, and PALB2 expression was compared with patient outcomes using Kaplan-Meier curves and the multivariate Cox regression model. PALB2-knockdown in PDAC cells had little effect on cell proliferation, but significantly decreased cell migration. Relatively high PALB2 expression was observed in PDAC tissues compared with in peritumoral tissues. Overall survival (OS) was negatively associated with PALB2 expression. TNM stage and PALB2 expression were identified as independent prognostic factors associated with OS via multivariate analysis. Overall, the present study demonstrated that PDAC cell migration was dependent on PALB2, which was further supported by the finding that elevated PALB2 expression in PDAC tissues was associated with poor survival in patients with PDAC. Therefore, PALB2 may serve as a novel prognostic marker in PDAC, which may aid with the development of therapeutic strategies for the disease.

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