Expression of PD-L1 and YWHAZ in Patients with Diffuse Large B Cell Lymphoma: A Possible Association with the Prognosis of Lymphoma

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common pathological subtype of non-Hodgkin lymphoma (NHL) and is the most common type of adult lymphoma. Due to the poor prognosis of relapsed/refractory DLBCL, new drug targets and therapeutic methods are urgently needed. We investigated the expression of programmed death ligand 1 (PD-L1) and 3-monooxygenase/tryptophan 5-monooxygenase activating protein zeta (14-3-3ζ or YWHAZ) in patients with DLBCL. The purpose was to verify the expression levels of YWHAZ and PD-L1 and their relationships with the prognosis of DLBCL and to lay a foundation for further study on the role of YWHAZ and PD-L1 in DLBCL. Immunohistochemistry was used in 140 patients with DLBCL to test protein expression levels of YWHAZ and PD-L1. All patients were followed up in the hospital or by telephone or via WeChat. The positive expression rate of YWHAZ was 62.14% (87/140). The expression was negatively correlated with the positive expression of BAD ( r = − 0.177 , P = 0.036 ) and positively correlated with the positive expression of BCL-2 ( r = 0.180 , P = 0.033 ). When the cut-off value for PD-L1 was established at 5%, 10%, 15%, and 20%, the corresponding positive expression rates of PD-L1 were 79.66% (94/118), 51.69% (61/118), 40.68% (48/118), and 36.44% (43/118). YWHAZ significantly affected the OS of DLBCL ( P ≤ 0.001 ). The prognosis of the patients was related to the positive expression of PD-L1 when the cut-off value of PD-L1 was 5% ( P = 0.033 ). However, positive expression of PD-L1 was not associated with the prognosis when the cut-off values of PD-L1 were 10% ( P = 0.404 ), 15% ( P = 0.208 ), and 20% ( P = 0.408 ). The positive expression of YWHAZ (hazard ratio 6.215; 95% confidence interval 3.214-12.017; P < 0.05 ) was an independent adverse prognostic factor for OS. YWHAZ may be an important oncogene in the occurrence and development of DLBCL and may be used as a therapeutic target. PD-L1 may be an oncogene or tumor suppressor gene in the occurrence and development of DLBCL. Different cut-off values of PD-L1 may affect the prognosis of DLBCL.

Structural Features and Physiological Associations of Human 14-3-3ζ Pseudogenes

“…At the cellular level, the current GTEx dataset includes only two cell types-fibroblasts and EBV-transformed lymphocytes. The expression level of 14-3-3ζ in both cells has functional consequences affecting disease outcomes [11,39,40]. When the relative expression of YWHAZ and pseudogenes is compared, the YWHAZ transcript is expressed at a high level in both fibroblasts and lymphocytes, while pseudogenes are expressed at much lower levels.…”

“…At the genetic level, the 14-3-3ζ (YWHAZ) gene is associated with human developmental delays, intellectual disability, epilepsy, dysmorphic features, amyotrophic lateral sclerosis, and heart diseases [19,40,[42][43][44][45][46] (Table 3). Genetic and transcriptomics studies show changes in 14-3-3ζ protein expression with several human diseases, including musculoskeletal, inflammation, and cancer [19,42,43,47].…”