PCK2, a SASP-Associated Gene, Serves as an Independent Prognostic Indicator in Diffuse Large B-Cell Lymphoma

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.

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.

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.

As a SASP-related gene, PCK2 serve as a candidate indicator providing supplementary information for DLBCL disease monitoring and prognostic assessment.