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Abstract：
Partner and localizer of BRCA2 (PALB2) is regarded as a colorectal cancer (CRC) risk gene, but the prognostic implication of PALB2 in CRC remains unclear. In this study, we evaluate the prognostic value of the gene copy number alteration (CNA) and mRNA expression of PALB2 in The Cancer Genome Atlas (TCGA) database, and then validated with our database. We downloaded the copy number and mRNA data of PALB2 from TCGA database and examined the relationship among the genetic alterations, expression levels and survival outcomes. Gene ontology (GO) analysis was performed to study the function of PALB2. cBioPortal database was used to explore the potential co-expression genes of PALB2. There were 6.3% (37 of 582) CRC patients diagnosed as PALB2 gene deletion. The PALB2 deletion group expressed significantly lower of PALB2 mRNA than the non-deletion group (P < 0.001). Survival analysis showed that PALB2 deletion was significantly associated with shorter disease-free survival (DFS) (P = 0.026) and overall survival (OS) (P = 0.028). Low mRNA expression of PALB2 correlated with shorter OS (P < 0.001). Multivariate analysis also confirmed that PALB2 deletion and low mRNA expression of PALB2 were independent prognostic factors of poor OS in CRC (P = 0.019, 0.034, respectively). In validation cohort, negative expression of PALB2 was associated with shorter OS (P = 0.006) in stage I patients. Multivariate analysis confirmed that negative expression of PALB2 was a poor-prognostic factor (P = 0.002). GO analysis and co-expression analysis investigated that PALB2 is primarily involved in the DNA repair process. These results suggest that PALB2 gene copy number deletion and low mRNA expression could be novel prognostic biomarkers for CRC.
摘要：
BRCA2（PALB2）的伴侣和定位基因被认为是结直肠癌（CRC）的风险基因，但PALB2在CRC中的预后意义尚不清楚.在这项研究中,我们评估了癌症基因组图谱（TCGA）数据库中PALB2基因拷贝数改变（CNA）和mRNA表达的预后价值，然后用我们的数据库验证。我们从TCGA数据库下载了PALB2的拷贝数和mRNA数据，并检查了遗传改变之间的关系，表达水平和生存结果。进行基因本体论(GO)分析以研究PALB2的功能。cBioPortal数据库用于探索PALB2的潜在共表达基因。6.3%(582例中的37例)CRC患者诊断为PALB2基因缺失。PALB2缺失组PALB2mRNA表达水平明显低于未缺失组(P<0.001)。生存分析显示,PALB2缺失与无病生存期(DFS)(P=0.026)和总生存期(OS)(P=0.028)显著相关。PALB2mRNA低表达与OS较短相关(P<0.001)。多因素分析也证实PALB2缺失和PALB2mRNA低表达是结直肠癌OS差的独立预后因素(分别为P=0.019、0.034)。在验证队列中，在I期患者中,PALB2阴性表达与OS较短相关(P=0.006).多因素分析证实PALB2阴性表达是预后不良因素(P=0.002)。GO分析和共表达分析研究了PALB2主要参与DNA修复过程。这些结果表明PALB2基因拷贝数缺失和低mRNA表达可能是CRC的新型预后生物标志物。
