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PCK2:衰老相关分泌表型(SASP)关联基因在弥漫性大B细胞淋巴瘤中的独立预后价值

 

Authors Chen M, Pan Y, Zhang J, Zeng Y 

Received 18 June 2025

Accepted for publication 6 November 2025

Published 20 November 2025 Volume 2025:18 Pages 16293—16313

DOI https://doi.org/10.2147/JIR.S548070

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Felix Marsh-Wakefield

Minggui Chen,1,* Yueyuan Pan,2,* Jinfang Zhang,3 Yan Zeng1 

1Department of Precision Clinical Laboratory, Zhanjiang Central Hospital, Guangdong Medical University (Central People’s Hospital of Zhanjiang), Zhanjiang, Guangdong, 524023, People’s Republic of China; 2Zhanjiang Institute of Clinical Medicine, Zhanjiang Central Hospital, Guangdong Medical University (Central People’s Hospital of Zhanjiang), Zhanjiang, Guangdong, 524023, People’s Republic of China; 3Department of Pathology, Shenzhen Nanshan People’s Hospital (NSPH), Shenzhen, Guangdong, 518052, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yan Zeng, Precision Clinical Laboratory, Central People’s Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, 524037, People’s Republic of China, Email yzeng910@163.com

Background: Diffuse large B-cell lymphoma (DLBCL) is characterised by substantial heterogeneity in phenotype and genetics. Recent studies have demonstrated that senescence-associated secretory phenotype (SASP) is both a tumor suppressor and a promoter of tumorigenesis and progression. However, reports on the effects of SASP on DLBCL remain limited. This study aimed to identify the SASP-related indicator of DLBCL, thereby providing new insights into the pathology of DLBCL.
Methods: Differential analysis and weighted co-expression network analysis (WGCNA) were applied to identify differentially expressed genes (DEGs) and key gene modules of DLBCL. Univariate Cox regression analysis was employed to identify SASP-related genes that serve as independent risk factors for DLBCL prognosis. Overlapped among three methods to obtain the hub gene and explore its potential mechanisms in DLBCL. The association between PCK2 and disease heterogeneity in DLBCL was further analyzed. We constructed a co-expression network centered on PCK2 and validated their expression and prognostic performance. Finally, 30 cases of tumour tissues were utilized to validate the expression of PCK2 in DLBCL patients by immunohistochemistry.
Results: In this study, through integrated bioinformatics methods, PCK2 was identified as a SASP-related gene in DLBCL. PCK2 can be regarded as a candidate indicator with good prognostic performance (AUC=0.953, Hazard Ratio (HR) =1.89, 95% CI=1.488– 2.399, p< 0.001). PCK2 was notably associated with multiple disease characteristics in DLBCL, particularly the immunosuppressive microenvironment and SASP signal. Furthermore, genes exhibiting high correlation with PCK2 demonstrated significant predictive value for DLBCL prognosis. Through immunohistochemistry, it was verified that PCK2 was markedly upregulated in DLBCL compared to normal controls.
Conclusion: As a SASP-related gene, PCK2 serve as a candidate indicator providing supplementary information for DLBCL disease monitoring and prognostic assessment.

Keywords: DLBCL, SASP, PCK2, Tumor immune microenvironment, Glycolysis