AbstractBranched-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.

摘要支链氨基酸转氨酶2（BCAT2）编码参与支链氨基酸（BCAA）分解代谢初始催化的关键蛋白，新出现的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索BCAT2，并评估其预后意义。

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.

我们利用多数据库方法，分析cBioPortal的遗传改变，来自TCGA和GTEx的RNA-Seq数据的表达模式，以及用于转录本分析的RSEM。使用人类蛋白质图谱，UniProt和STRING评估蛋白质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平台检查各种癌症的免疫细胞浸润。

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.

我们的结果显示，BCAT2改变主要是扩增，并且在各种肿瘤中上调，与几种肿瘤类型（包括GBMLGG，LGG和UVM）的较差存活率相关。BCAT2蛋白水平升高在泛癌中很常见，与一系列代谢酶相互作用。

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..

此外，BCAT2表达显着影响CD4+T细胞，CD8+T细胞和Treg细胞的浸润，在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，可能调节关键的代谢和免疫因子以介导肿瘤进展和微环境。。

IntroductionCancer remains a foremost cause of death and a substantial public health challenge worldwide, directly impacting both healthcare systems and the global economy1. Despite advancements in primary treatment strategies such as surgery, radiotherapy, and chemotherapy2, patients frequently face poor prognoses and survival, hindered by complications such as drug resistance and side effects3.

引言癌症仍然是全球最主要的死亡原因和重大的公共卫生挑战，直接影响医疗保健系统和全球经济1。尽管手术，放疗和化疗等主要治疗策略取得了进展2，但患者经常面临预后和生存率差的问题，受到耐药性和副作用等并发症的阻碍3。

This underscores the urgent need for novel biomarkers as therapeutic and diagnostic targets. Pan-cancer analysis, transcending traditional organ-specific approaches, offers a comprehensive perspective by integrating genomics data across various cancer types. This approach is crucial for identifying biomarker genes.

。泛癌分析超越了传统的器官特异性方法，通过整合各种癌症类型的基因组学数据，提供了一个全面的视角。这种方法对于鉴定生物标志物基因至关重要。

By discovering and validating these biomarkers, pan-cancer analysis holds the potential to revolutionize cancer prognosis, treatment, and the understanding of cancer biology4.Given these challenges, our study focuses on the metabolic pathways involving branched-chain amino acids (BCAAs), specifically examining the role of branched-chain amino acid transaminase 2 (BCAT2) within a pan-cancer framework.

通过发现和验证这些生物标志物，泛癌分析有可能彻底改变癌症的预后，治疗和对癌症生物学的理解4。鉴于这些挑战，我们的研究集中在涉及支链氨基酸（BCAAs）的代谢途径上，特别是在泛癌框架内检查支链氨基酸转氨酶2（BCAT2）的作用。

We hypothesize that BCAT2 could serve as a critical biomarker, offering new insights into cancer prognosis and therapeutic strategies.Branched-chain amino acids (BCAAs)—leucine, valine, and isoleucine—are essential hydrophobic amino acids predominantly metabolized in muscle tissues5. Under normal circumstances, BCAAs participate in protein synthesis and molecular signal regulations by mediating the production of coenzyme A (CoA) and glutamate6.

我们假设BCAT2可以作为一个关键的生物标志物，为癌症预后和治疗策略提供新的见解。支链氨基酸（BCAAs）-亮氨酸，缬氨酸和异亮氨酸是主要在肌肉组织中代谢的必需疏水性氨基酸5。在正常情况下，BCAAs通过介导辅酶A（CoA）和谷氨酸6的产生参与蛋白质合成和分子信号调节。

Recently, anomalous BCAAs metabolism was found in multiple tumors accompanied by disturbed nitrogen and carbon sources, leading tumor cells to obtain BCAAs from other circulation or peripheral tissues7,8. Emerging evidence highlig.

最近，在多个肿瘤中发现异常的BCAAs代谢伴随着氮源和碳源的紊乱，导致肿瘤细胞从其他循环或外周组织获得BCAAs 7,8。新出现的证据很高。

Data availability statement

BCAT2 expression and clinical data across various cancers were sourced from The Cancer Genome Atlas (TCGA, https://www.cancer.gov/tcga) and Genotype-Tissue Expression (GTEx, http://commonfund.nih.gov/GTEx), via the Genomic Data Commons (GDC, https://gdc.cancer.gov/). BCAT2 genomic alterations data were obtained from the cBioPortal database (http://www.cbioportal.org/).

BCAT2在各种癌症中的表达和临床数据均来自癌症基因组图谱（TCGA，https://www.cancer.gov/tcga)和基因型组织表达（GTEx，http://commonfund.nih.gov/GTEx)，通过基因组数据共享（GDC，https://gdc.cancer.gov/)。BCAT2基因组改变数据来自cBioPortal数据库(http://www.cbioportal.org/)。

Protein expression analysis, including interaction networks and subcellular localization, was conducted using The Human Protein Atlas (https://www.proteinatlas.org/), STRING database (https://cn.string-db.org/), and UniProt (https://www.uniprot.org/)..

使用人类蛋白质图谱进行蛋白质表达分析，包括相互作用网络和亚细胞定位(https://www.proteinatlas.org/)(https://cn.string-db.org/)和UniProt(https://www.uniprot.org/)。。

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Download referencesAuthor informationAuthors and AffiliationsSchool of Public Health, Chongqing Medical University, Chongqing, 400016, ChinaQixuan Cao, Jie Fan, Jian Zou & Wei WangAuthorsQixuan CaoView author publicationsYou can also search for this author in

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PubMed谷歌学术贡献。C、 J.F.整理了数据，分析了结果，并创建了可视化。Q、 C.写了原稿。J、 Z.和W.W.审查并编辑了手稿并监督了该项目。通讯作者通讯

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Reprints and permissionsAbout this articleCite this articleCao, Q., Fan, J., Zou, J. et al. Multi-omics analysis identifies BCAT2 as a potential pan-cancer biomarker for tumor progression and immune microenvironment modulation.

转载和许可本文引用本文Cao，Q.，Fan，J.，Zou，J。等人。多组学分析将BCAT2鉴定为肿瘤进展和免疫微环境调节的潜在泛癌生物标志物。

Sci Rep 14, 23371 (2024). https://doi.org/10.1038/s41598-024-74441-1Download citationReceived: 17 May 2024Accepted: 26 September 2024Published: 08 October 2024DOI: https://doi.org/10.1038/s41598-024-74441-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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