Ge Ouyang, Huang Anle, Wang Xin, Chen Yuling, Ye Yuanchun, Schomburg Lutz
Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, D-13353 Berlin, Germany.
Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China.
Oncol Lett. 2021 Mar;21(3):224. doi: 10.3892/ol.2021.12485. Epub 2021 Jan 24.
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.
在DNA修复过程中,BRCA1和BRCA2与BRCA2的肿瘤抑制伴侣及定位蛋白(PALB2)相互作用。PALB2突变与乳腺癌和卵巢癌风险增加相关,而PALB2表达上调与临床预后不良相关。本研究调查了PALB2在胰腺导管腺癌(PDAC)中的作用及预后价值。在PDAC细胞系中使用小干扰RNA抑制PALB2表达,并研究其对细胞增殖和迁移的后续影响。通过免疫组织化学分析了157例行胰十二指肠切除术治疗PDAC患者的组织芯片,并使用Kaplan-Meier曲线和多变量Cox回归模型将PALB2表达与患者预后进行比较。PDAC细胞中PALB2基因敲低对细胞增殖影响不大,但显著降低了细胞迁移。与癌旁组织相比,在PDAC组织中观察到相对较高的PALB2表达。总生存期(OS)与PALB2表达呈负相关。通过多变量分析确定TNM分期和PALB2表达为与OS相关的独立预后因素。总体而言,本研究表明PDAC细胞迁移依赖于PALB2,PDAC组织中PALB2表达升高与PDAC患者生存率低相关这一发现进一步支持了该结论。因此,PALB2可能作为PDAC的一种新型预后标志物,这可能有助于开发该疾病的治疗策略。