In a recent study, researchers identified potential links between prognosis with diffuse large B-cell lymphoma (DLBCL) and the expression of programmed death ligand 1 (PD-L1) and another protein called 3-monooxygenase/tryptophan 5-monooxygenase activating protein zeta (YWHAZ). The researchers presented their findings in the Journal of Immunology Research.
Challenges in management of relapsed/refractory DLBCL suggest possible roles for additional therapeutic targets for this condition, the researchers indicated in their report. The research team, based in China, conducted this study to build on earlier studies that have suggested possible connections between YWHAZ or PD-L1 expression and DLBCL prognosis.
The research team evaluated demographic data from patients with DLBCL, in addition to the results of several laboratory and imaging analyses from these patients. Biopsy samples obtained from patients were analyzed through microarray and immunohistochemistry approaches and the researchers evaluated findings from these analyses in the context of survival outcomes in patients.
There were 140 patients included in the analysis, with a median age of 59 years, and 45.71% of patients had an age of 60 or more years. Extranodal DLBCL was found in 46 patients, while 94 had nodal DLBCL.
Immunohistochemistry analysis revealed YWHAZ expression in the majority of patients (62.14%). YWHAZ expression showed a significant relationship with worse overall survival (OS) with DLBCL in univariate analysis (P ≤.001). Additionally, in multivariate analysis of OS, positive YWHAZ expression was considered an independent adverse prognostic factor (hazard ratio, 6.215; 95% CI, 3.214-12.017; P <.05).
Other analyses indicated that YWHAZ expression may be associated with expression of other potentially relevant proteins. These included a positive correlation with BCL-2 protein expression (P =.033) and a negative correlation with BAD protein expression (P =.036), among other patterns.
Positive PD-L1 expression appeared linked to prognosis with DLBCL only at a threshold of 5% expression in univariate analysis (P =.033); expression levels evaluated at thresholds of 10%, 15%, and 20% did not show significant relationships with DLBCL prognosis. Among 118 patients analyzed for PD-L1 expression, 79.66% showed positive PD-L1 expression at a cut-off of 5%.
“YWHAZ may be an important oncogene in the occurrence and development of DLBCL and may be used as a therapeutic target,” the researchers wrote in their report. They continued, “PD-L1 may be an oncogene or tumor suppressor gene in the occurrence and development of DLBCL.” However, they noted that varied thresholds of PD-L1 expression may show different connections to DLBCL prognosis. Overall, the researchers considered the study’s results supportive of possible new targets for DLBCL diagnosis and treatment.
Yan S, Shang Q, Fan Z, et al. Expression of PD-L1 and YWHAZ in patients with diffuse large B cell lymphoma: a possible association with the prognosis of lymphoma. J Immunol Res. 2022;2022:5633096. doi:10.1155/2022/5633096