Pan Weiyu, Lu Kui, Wang Weixia, Yao Junxia, Hou Yingyong
Department of Pathology, Qingpu Branch of Zhongshan Hospital, Fudan University, No. 1158 East Park Road, Qingpu District, Shanghai 200032, PR China.
Department of Pathology, Qingpu Branch of Zhongshan Hospital, Fudan University, No. 1158 East Park Road, Qingpu District, Shanghai 200032, PR China.
Comput Biol Chem. 2020 May 20;87:107289. doi: 10.1016/j.compbiolchem.2020.107289.
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.
乳腺癌2号基因的伙伴和定位蛋白（PALB2）被视为一种结直肠癌（CRC）风险基因，但PALB2在CRC中的预后意义仍不清楚。在本研究中，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，然后用我们自己的数据库进行验证。我们从TCGA数据库下载了PALB2的拷贝数和mRNA数据，并研究了基因改变、表达水平和生存结果之间的关系。进行基因本体（GO）分析以研究PALB2的功能。使用cBioPortal数据库探索PALB2的潜在共表达基因。有6.3%（582例中的37例）CRC患者被诊断为PALB2基因缺失。PALB2缺失组的PALB2 mRNA表达明显低于非缺失组（P < 0.001）。生存分析表明，PALB2缺失与无病生存期（DFS）显著缩短（P = 0.026）和总生存期（OS）显著缩短（P = 0.028）相关。PALB2的低mRNA表达与较短的OS相关（P < 0.001）。多变量分析也证实，PALB2缺失和PALB2的低mRNA表达是CRC患者OS不良的独立预后因素（分别为P = 0.019、0.034）。在验证队列中，PALB2的阴性表达与I期患者较短的OS相关（P = 0.006）。多变量分析证实，PALB2的阴性表达是一个不良预后因素（P = 0.002）。GO分析和共表达分析表明，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新的预后生物标志物。
