Amino Acid Metabolism-Related Gene Kynureninase (KYNU) as a Prognostic Predictor and Regulator of Diffuse Large B-Cell Lymphoma.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2025-02-11 DOI:10.1007/s10528-025-11047-w

Yu Zhang, Shi Feng, Liemei Lv, Cong Wang, Ran Kong, Guangcai Zhong, Na Wang, Peipei Li, Xiangxiang Zhou

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Abstract

Dysregulation of amino acid metabolism is recognized to have a substantial influence on tumorigenesis and the modulation of tumor microenvironment. However, the role of amino acid metabolism-related genes in diffuse large B-cell lymphoma (DLBCL) remains undefined. Therefore, we aimed to explore the influence of amino acid metabolism-related genes in DLBCL using bioinformatics approaches. Consensus clustering demonstrated that the reprogramming of amino acid metabolism has prognostic value in DLBCL. Subsequently, we developed a risk model using LASSO-Cox regression analysis to accurately predict DLBCL prognosis and identified kynureninase (KYNU) as a potentially valuable biomarker. Analysis of immune infiltration was conducted to examine the correlation between risk scores and immune profiles. Furthermore, RT-qPCR showed that the KYNU mRNA levels were upregulated in OCI-LY1, OCI-LY3, and OCI-LY10 DLBCL cells compared with normal CD19+B lymphocytes. Cell proliferation assays and flow cytometry analysis showed that inhibition of KYNU expression reduced cell proliferation and induced apoptosis of DLBCL cells. Overall, we demonstrated the significant impact of amino acid metabolism on DLBCL. Our findings may help improve the assessment of disease prognosis and provide potential therapeutic strategies for DLBCL.

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氨基酸代谢失调被认为对肿瘤发生和肿瘤微环境调控有重大影响。然而，氨基酸代谢相关基因在弥漫大 B 细胞淋巴瘤（DLBCL）中的作用仍未确定。因此，我们旨在利用生物信息学方法探讨氨基酸代谢相关基因对弥漫性大B细胞淋巴瘤的影响。共识聚类表明，氨基酸代谢的重编程在DLBCL中具有预后价值。随后，我们利用LASSO-Cox回归分析建立了一个风险模型，以准确预测DLBCL的预后，并发现犬尿氨酸酶（KYNU）是一个潜在的有价值的生物标志物。对免疫浸润进行了分析，以研究风险评分与免疫特征之间的相关性。此外，RT-qPCR显示，与正常CD19+B淋巴细胞相比，OCI-LY1、OCI-LY3和OCI-LY10 DLBCL细胞的KYNU mRNA水平上调。细胞增殖测定和流式细胞术分析表明，抑制 KYNU 的表达可减少 DLBCL 细胞的增殖并诱导其凋亡。总之，我们证明了氨基酸代谢对 DLBCL 的重大影响。我们的发现可能有助于改善对疾病预后的评估，并为 DLBCL 提供潜在的治疗策略。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.