PD-L1/CD274 and miR-155/MIR155HG Genetic Variants as Prognostic and Risk Biomarkers in Diffuse Large B-Cell Lymphoma

<b>Background/Objectives</b>: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, for which predicting clinical outcomes remains challenging. Although immune-checkpoint pathways are known to influence tumor biology, the impact of their germline variants on DLBCL susceptibility and prognosis has not been fully elucidated. <b>Methods</b>: Variants in PD-L1 gene <i>CD274</i> (rs4143815, rs822336), and miR-155 gene <i>MIR155HG</i> (rs767649, rs1893650), assessed by TaqMan assays in 99 DLBCL patients and 113 age- and sex-matched healthy controls, were associated with clinicopathological features, treatment response, overall survival (OS), relapse-free survival (RFS), and disease susceptibility. <b>Results</b>: The PD-L1 variant rs822336 was significantly associated with relapse status (<i>p</i> = 0.005) and RFS (<i>p</i> = 0.008), with the wild-type GG genotype showing the poorest RFS that remained independent in the multivariate Cox analysis (HR = 2.387, <i>p</i> = 0.003). Conversely, rs4143815 showed a nominal association with treatment resistance (<i>p</i> = 0.026), while patients carrying the GG genotype had worse OS (<i>p</i> = 0.006). In susceptibility analyses, miR-155 variant rs767649 showed a nominal association with DLBCL risk, with the rare AA genotype showing an increased risk of DLBCL (OR = 5.234, <i>p</i> = 0.045), which did not remain significant after Bonferroni correction. <b>Conclusions</b>: In a hypothesis-generating manner, these findings suggest that PD-L1 genetic variants may predominantly influence disease progression and outcomes, while miR-155 variation may contribute to DLBCL susceptibility. These findings highlight germline immunogenetic variants as stable, treatment-independent markers that may inform future studies on risk stratification and prognosis in DLBCL.