The critical role of BAP1 mutation in the prognosis and treatment selection of kidney renal clear cell carcinoma
The critical role of BAP1 mutation in the prognosis and treatment selection of kidney renal clear cell carcinoma
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DOI：
10.21037/tau-20-1079
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发表时间：
2020-08-01
影响因子：
2
通讯作者：
Wu, Aiming
中科院分区：
文献类型：
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作者：
Tan, Guobin;Xuan, Zijun;Wu, Aiming
背景：BAP1 突变是肾透明细胞癌 (KIRC) 中常见的突变，也是个体化治疗的潜在生物标志物。我们评估了 BAP1 突变在 KIRC 预后和治疗中的临床意义。本研究还鉴定了与这些机制相关的潜在关键通路和相关基因。方法：我们在cBioPortal上鉴定了BAP1突变患者的相关数据，并在癌症药物敏感性基因组学（GDSC）上鉴定了对BAP1突变具有显着选择性的化合物。然后，我们通过GSEA分析确定了突变型和野生型BAP1患者之间生物学功能注释和通路的mRNA表达水平的差异。此外，我们筛选了 KIRC 患者中 BAP1 突变型和野生型之间的差异表达基因（DEG），并进行了 GO 和 KEGG 分析。最后，我们建立了蛋白质-蛋白质相互作用 (PPI) 网络来研究候选 DEG 编码的蛋白质之间的相互作用。结果：TCGA 数据审查显示 41 名 KIRC 患者 (10%) 表现出 BAP1 突变。进一步分析发现了 730 个 DEG，其中 617 个基因被下调，其中 113 个基因被上调。 GO和KEGG通路分析表明DEGs富含代谢、药物代谢细胞色素P450和药物代谢酶。随后，确定了 PPI 网络中按程度排名的前 10 个枢纽基因。此外，我们的研究结果证实，BAP1 突变与 KIRC 患者预后恶化相关。此外，对GDSC数据库的分析显示，具有BPP1突变的KIRC患者更容易对林赛替尼产生反应。结论：我们的研究确定了KIRC中与BAP1突变相关的主要通路和相关基因，这有助于制定靶向治疗策略以增强KIRC的预后预测。
Background: The BAP1 mutation is commonly found kidney renal clear cell carcinoma (KIRC) and a potential biomarker of individualized therapy. We evaluated the clinical significance of BAP1 mutation in the prognosis and treatment therapies for KIRC. Potential key pathways and related genes associated with these mechanisms were also identified in this investigation.Methods: We identified the relevant data of patients BAP1 mutated on the cBioPortal and the compounds with significant selectivity to BAP1 mutations on the Genomics of Drug Sensitivity in Cancer (GDSC). And then, we identified the differences in mRNA expression levels of biological function annotation and pathways between mutated and wild type BAP1 patients by GSEA analysis. Furthermore, we screened the differentially expressed genes (DEGs) between BAP1 mutated and wild typed in KIRC patients and performed the GO and KEGG analysis. Finally, we conducted a protein-protein interaction (PPI) network to investigate the interaction between proteins encoded by candidate DEGs.Results: Review of the TCGA data revealed 41 patients (10%) with KIRC displayed the BAP1 mutation. Further analysis led to the identification of 730 DEGs, while 617 genes were shown to be down-regulated, with 113 genes displaying upregulation. GO and KEGG pathway analysis indicated DEGs as enriched in metabolism, drug metabolism-cytochrome P450, and Drug-metabolizing enzymes. Subsequently, the top 10 hub genes, ranked by the degree in the PPI network were identified. Furthermore, our findings verify that the BAP1 mutation was associated with the deterioration of prognosis in patients with KIRC. Additionally, analysis of the GDSC database revealed that KIRC patients with BPP1 mutation are more prone to responding to Linsitinib.Conclusions: Our investigation identified the main pathways and relevant genes related to the BAP1 mutation in KIRC, which can contribute to the development of targeted treatment strategies for enhanced prognostic predictions of KIRC.