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

Area of Science:

• Immunogenetics
• Oncology
• Molecular Biology

Background:

• Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with challenging prognostication.
• The role of germline variants in immune-checkpoint genes, such as PD-L1 and miR-155, in DLBCL is not fully understood.
• Investigating these variants could reveal new markers for DLBCL risk and patient outcomes.

Purpose of the Study:

• To investigate the association between germline variants in the PD-L1 gene (CD274) and miR-155 gene (MIR155HG) with DLBCL susceptibility and prognosis.
• To determine if these genetic variants correlate with clinical features, treatment response, overall survival (OS), and relapse-free survival (RFS) in DLBCL patients.

Main Methods:

• Genotyping of PD-L1 variants (rs4143815, rs822336) and miR-155 variants (rs767649, rs1893650) using TaqMan assays.
• Analysis of 99 DLBCL patients and 113 healthy controls.
• Statistical association of variants with clinicopathological data, treatment response, OS, RFS, and DLBCL susceptibility.

Main Results:

• The PD-L1 variant rs822336 was significantly associated with poorer relapse-free survival (RFS) and relapse status, independent of other factors.
• The PD-L1 variant rs4143815 showed a nominal association with treatment resistance and worse overall survival (OS) in the GG genotype.
• The miR-155 variant rs767649 (AA genotype) showed a nominal association with increased DLBCL risk, though not significant after correction.

Conclusions:

• Germline PD-L1 variants appear to significantly influence DLBCL progression and patient outcomes, potentially serving as prognostic markers.
• Germline miR-155 variation may contribute to DLBCL susceptibility.
• These findings suggest germline immunogenetic variants are stable, treatment-independent markers for future DLBCL risk stratification and prognosis studies.