Ju Qiang, Li Xin-Mei, Zhang Heng, Zhao Yan-Jie
Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
School of Public Health, Qingdao University, Qingdao, China.
Front Mol Biosci. 2020 Nov 2;7:573619. doi: 10.3389/fmolb.2020.573619. eCollection 2020.
BRCA1-associated protein (BRAP) is a critical gene that regulates inflammation-related signaling pathway and affects patients' prognosis in esophageal squamous cell carcinoma (ESCC). However, its roles in different cancers remain largely unknown.
BRAP expression in human pan-cancer was analyzed the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to evaluate the association between BRAP expression with mismatch repair (MMR) gene mutation and DNA methyltransferase. We evaluated the influence of BRAP on clinical prognosis by univariate survival analysis. Moreover, the correlation between BRAP and tumor immune infiltration was analyzed the Tumor Immune Evaluation Resource (TIMER) database. Pearson correlation analysis was used to investigate the correlation between BRAP expression and immune checkpoint genes expression.
BRAP is abnormally overexpressed and significantly correlated with MMR gene mutation level and DNA methyltransferase expression in human pan-cancer. Univariate survival analysis showed that BRAP was significant with patients' overall survival (OS) in six cancer types, disease-free interval (DFI) in three cancer types, and progression-free interval (PFI) in two cancer types. Remarkably, increased BRAP expression was strongly correlated with patients' poor prognosis in liver hepatocellular carcinoma (LIHC), whether OS ( < 0.0001, hazard ratio (HR) = 1.1), DFI ( = 0.00099, HR = 1.06), or PFI ( = 0.00025, HR = 1.07). Moreover, a positive relationship was found between BRAP expression and immune infiltrating cells including B cell, CD4 + T cell, CD8 + T cell, dendritic cell, macrophage cell, and neutrophil cell in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and LIHC. Additionally, BRAP expression showed strong correlations with immune checkpoint genes in LIHC.
BRAP expression is increased in human pan-cancer samples compared with normal tissues. Overexpression of BRAP is correlated with poor prognosis and immune infiltration in multiple cancers, especially in LIHC. These findings suggest that BRAP may be used as a potential molecular biomarker for determining prognosis and immune infiltration in LIHC.
BRCA1相关蛋白（BRAP）是一个关键基因，可调节炎症相关信号通路并影响食管鳞状细胞癌（ESCC）患者的预后。然而，其在不同癌症中的作用仍 largely 未知。
利用基因型-组织表达（GTEx）和癌症基因组图谱（TCGA）数据库分析BRAP在人类泛癌中的表达。采用Pearson相关分析评估BRAP表达与错配修复（MMR）基因突变和DNA甲基转移酶之间的关联。通过单因素生存分析评估BRAP对临床预后的影响。此外，利用肿瘤免疫评估资源（TIMER）数据库分析BRAP与肿瘤免疫浸润之间的相关性。采用Pearson相关分析研究BRAP表达与免疫检查点基因表达之间的相关性。
BRAP在人类泛癌中异常过表达，且与MMR基因突变水平和DNA甲基转移酶表达显著相关。单因素生存分析表明，BRAP在六种癌症类型中与患者总生存期（OS）显著相关，在三种癌症类型中与无病生存期（DFI）显著相关，在两种癌症类型中与无进展生存期（PFI）显著相关。值得注意的是，在肝细胞癌（LIHC）中，BRAP表达增加与患者预后不良密切相关，无论是OS（<0.0001，危险比（HR）=1.1）、DFI（=0.00099，HR = 1.06）还是PFI（=0.00025，HR = 1.07）。此外，在结肠腺癌（COAD）、肾透明细胞癌（KIRC）和LIHC中，发现BRAP表达与包括B细胞、CD4 + T细胞、CD8 + T细胞、树突状细胞、巨噬细胞和中性粒细胞在内的免疫浸润细胞呈正相关。此外，BRAP表达在LIHC中与免疫检查点基因呈强相关。
与正常组织相比，人类泛癌样本中BRAP表达增加。BRAP过表达与多种癌症，尤其是LIHC中的不良预后和免疫浸润相关。这些发现表明，BRAP可能作为一种潜在的分子生物标志物，用于确定LIHC中的预后和免疫浸润。
