深入了解 BRIP1 在泛癌中的致癌、预后和免疫学作用：一项基于数据挖掘的综合研究,Journal of Oncology

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深入了解 BRIP1 在泛癌中的致癌、预后和免疫学作用：一项基于数据挖掘的综合研究
Journal of Oncology Pub Date : 2023-4-28 , DOI: 10.1155/2023/4104639
Yongru Liu ₁ , Xi Wu ₁ , Yunlu Feng ₁ , Qingwei Jiang ₁ , Shengyu Zhang ₁ , Qiang Wang ₁ , Aiming Yang ₁

Affiliation

背景。BRCA1 相互作用解旋酶 1 (BRIP1) 是一种 ATP 依赖性 DNA 解旋酶，属于具有 DEAH 结构域的铁-硫 (Fe-S) 解旋酶簇家族，在 DNA 损伤和修复、范可尼贫血和几种癌症，包括乳腺癌和卵巢癌。然而，它在泛癌中的作用在很大程度上仍然未知。方法. 肿瘤和正常组织的 BRIP1 表达数据从癌症基因组图谱、基因型组织表达和人类蛋白质图谱数据库下载。进一步分析了 BRIP1 与预后、基因组改变、拷贝数变异 (CNV) 以及泛癌甲基化之间的相关性。进行蛋白质-蛋白质相互作用 (PPI) 和基因集富集和变异分析（GSEA 和 GSVA）以确定 BRIP1 的潜在途径和功能。此外，还探讨了BRIP1与肿瘤微环境（TME）、免疫浸润、免疫相关基因、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、免疫治疗和抗肿瘤药物在泛癌中的相关性。结果. 差异分析显示 BRIP1 在 28 种癌症类型中的表达增加，其异常表达可能是大多数癌症预后的指标。在泛癌BRIP1的各种突变类型中，扩增是最常见的类型。BRIP1 表达分别与 23 种肿瘤类型和 16 种肿瘤类型中的 CNV 和 DNA 甲基化显着相关。PPI、GSEA 和 GSVA 结果验证了 BRIP1 与 DNA 损伤和修复、细胞周期和新陈代谢之间的关联。此外，证实了BRIP1的表达及其与TME、免疫浸润细胞、免疫相关基因、TMB、MSI以及多种抗肿瘤药物和免疫治疗的相关性。结论. 我们的研究表明，BRIP1 在各种肿瘤的发生和免疫中起着不可或缺的作用。它不仅可以作为诊断和预后生物标志物，还可以作为泛癌抗肿瘤治疗过程中药物敏感性和免疫反应的预测指标。

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Insights into the Oncogenic, Prognostic, and Immunological Role of BRIP1 in Pan-Cancer: A Comprehensive Data-Mining-Based Study

Background. BRCA1 interacting helicase 1 (BRIP1), an ATP-dependent DNA helicase which belongs to an Iron-Sulfur (Fe-S) helicase cluster family with a DEAH domain, plays a key role in DNA damage and repair, Fanconi anemia, and development of several cancers including breast and ovarian cancer. However, its role in pan-cancer remains largely unknown. Methods. BRIP1 expression data of tumor and normal tissues were downloaded from the Cancer Genome Atlas, Genotype-Tissue Expression, and Human Protein Atlas databases. Correlation between BRIP1 and prognosis, genomic alterations, and copy number variation (CNV) as well as methylation in pan-cancer were further analyzed. Protein-protein interaction (PPI) and gene set enrichment and variation analysis (GSEA and GSVA) were performed to identify the potential pathways and functions of BRIP1. Besides, BRIP1 correlations with tumor microenvironment (TME), immune infiltration, immune-related genes, tumor mutation burden (TMB), microsatellite instability (MSI), and immunotherapy as well as antitumor drugs were explored in pan-cancer. Results. Differential analyses showed an increased expression of BRIP1 in 28 cancer types and its aberrant expression could be an indicator for prognosis in most cancers. Among the various mutation types of BRIP1 in pan-cancer, amplification was the most common type. BRIP1 expression had a significant correlation with CNV and DNA methylation in 23 tumor types and 16 tumor types, respectively. PPI, GSEA, and GSVA results validated the association between BRIP1 and DNA damage and repair, cell cycle, and metabolism. In addition, the expression of BRIP1 and its correlation with TME, immune-infiltrating cells, immune-related genes, TMB, and MSI as well as a variety of antitumor drugs and immunotherapy were confirmed. Conclusions. Our study indicates that BRIP1 plays an imperative role in the tumorigenesis and immunity of various tumors. It may not only serve as a diagnostic and prognostic biomarker but also can be a predictor for drug sensitivity and immunoreaction during antitumor treatment in pan-cancer.

更新日期：2023-04-28

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