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

  • Biochem Genet. 2025 Feb 11. doi: 10.1007/s10528-025-11047-w.
Yu Zhang  #  1 ,  Shi Feng  #  2 ,  Liemei Lv  3 ,  Cong Wang  1 ,  Ran Kong  3 ,  Guangcai Zhong  1 ,  Na Wang  1 ,  Peipei Li  1 ,  Xiangxiang Zhou  4  5  6
Affiliations
  • 1. Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
  • 2. School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
  • 3. Department of Hematology, Shandong Provincial Hospital, Shandong University, No.324, Jingwu Road, Jinan, 250021, Shandong, China.
  • 4. Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. [email protected].
  • 5. Department of Hematology, Shandong Provincial Hospital, Shandong University, No.324, Jingwu Road, Jinan, 250021, Shandong, China. [email protected].
  • 6. Branch of National Clinical Research Center for Hematologic Diseases, Jinan, 250021, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 39932613 DOI: 10.1007/s10528-025-11047-w
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.

Keywords
Amino acid metabolism; DLBCL; Immune therapy; Prognosis; Tumor microenvironment.
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