Abstract
BackgroundBRCA1-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.MethodsBRAP expression in human pan-cancer was analyzed via 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 via the Tumor Immune Evaluation Resource (TIMER) database. Pearson correlation analysis was used to investigate the correlation between BRAP expression and immune checkpoint genes expression.ResultsBRAP 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 (P < 0.0001, hazard ratio (HR) = 1.1), DFI (P = 0.00099, HR = 1.06), or PFI (P = 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.ConclusionBRAP 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.
Highlights
MATERIALS AND METHODSBRCA1-associated protein (BRAP) was first reported to bind to breast cancer suppressor protein BRCA1
We found that BRAP expression was higher in 25 tumors including ACC, BLCA, BRCA, CESC, CHOL, COAD, ESCA, GBM, HNSC, KICH, KIRC, KIRP, LAML, LGG, LIHC, LUAD, LUSC, OV, PAAD, PRAD, READ, SKCM, STAD, THCA, and UCS than in normal tissues (Figure 1D)
These results indicate that BRAP is abnormally overexpressed in human pan-cancer
Summary
MATERIALS AND METHODSBRCA1-associated protein (BRAP) was first reported to bind to breast cancer suppressor protein BRCA1. Immune-related mechanisms play important roles in multiple pathophysiological progresses (Rožman, 2018; Gonzalo and Coll-Bonfill, 2019; Walker et al, 2019), and immunotherapeutic strategies are considered as a promising direction for the treatment of many cancers (Washah et al, 2020). Immunotherapy, such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, plays a good anti-tumor effect in the treatment of malignant tumors, such as lung cancer (Cheng et al, 2020; Eguren-Santamaria et al, 2020) and melanoma (Cuevas and Daud, 2018; Albershardt et al, 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).
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