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多组学分析鉴定 BCAT2 为一种潜在的泛癌肿瘤进展和免疫微环境调节的生物标志物。

Multi-omics analysis identifies BCAT2 as a potential pan-cancer biomarker for tumor progression and immune microenvironment modulation.

机构信息

School of Public Health, Chongqing Medical University, Chongqing, 400016, China.

出版信息

Sci Rep. 2024 Oct 8;14(1):23371. doi: 10.1038/s41598-024-74441-1.

Abstract

Branched-chain amino acid transaminase 2 (BCAT2) encodes a crucial protein involved in the initial catalysis of branched-chain amino acid (BCAA) catabolism, with emerging evidence suggesting its association with tumor progression. This study explores BCAT2 in a pan-cancer multi-omics context and evaluates its prognostic significance. We utilized a multi-database approach, analyzing cBioPortal for genetic alterations, RNA-Seq data from TCGA and GTEx for expression patterns, and RSEM for transcript analysis. Protein expression and interaction networks were assessed using the Human Protein Atlas, UniProt, and STRING. Prognostic value was determined through Cox regression analysis of TCGA clinical survival data, while immune cell infiltration across various cancers was examined using TCGA data and the TIMER2 platform. Our results revealed that BCAT2 alterations are primarily amplifications and is upregulated in various tumors, correlating with poor survival rates in several tumor types, including GBMLGG, LGG, and UVM. Elevated BCAT2 protein levels were common in pan-cancer, interacting with a range of metabolic enzymes. Additionally, BCAT2 expression significantly influenced CD4+ T cells, CD8+ T cells, and Treg cells infiltration, with varied correlations across cancer types. These findings indicate BCAT2 as a potential biomarker for cancer diagnosis and therapy, potentially regulating key metabolic and immune factors to mediate tumor progression and the microenvironment.

摘要

支链氨基酸转氨酶 2(BCAT2)编码一种参与支链氨基酸(BCAA)分解代谢初始催化的关键蛋白,有新证据表明其与肿瘤进展有关。本研究在泛癌多组学背景下探讨 BCAT2,并评估其预后意义。我们采用多数据库方法,在 cBioPortal 分析遗传改变,在 TCGA 和 GTEx 分析 RNA-Seq 数据以了解表达模式,在 RSEM 分析转录分析。使用 Human Protein Atlas、UniProt 和 STRING 评估蛋白表达和相互作用网络。通过 TCGA 临床生存数据的 Cox 回归分析确定预后价值,同时使用 TCGA 数据和 TIMER2 平台研究各种癌症中的免疫细胞浸润情况。我们的结果表明,BCAT2 改变主要是扩增,在各种肿瘤中上调,与包括 GBMLGG、LGG 和 UVM 在内的几种肿瘤类型的生存率降低相关。BCAT2 蛋白水平在泛癌中升高,与一系列代谢酶相互作用。此外,BCAT2 表达显著影响 CD4+T 细胞、CD8+T 细胞和 Treg 细胞浸润,在不同癌症类型中具有不同的相关性。这些发现表明 BCAT2 是癌症诊断和治疗的潜在生物标志物,可能通过调节关键代谢和免疫因子来介导肿瘤进展和微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f3/11458862/3df17f2504fc/41598_2024_74441_Fig1_HTML.jpg

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