Identification of PLA2G7 as a novel biomarker of diffuse large B cell lymphoma

Abstract

Background Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma globally, and patients with relapsed or refractory DLBCL typically experience poor long-term outcomes. Methods Differentially expressed genes associated with DLBCL were identified using two GEO datasets in an effort to detect novel diagnostic or prognostic biomarkers of this cancer type, after which receiver operating characteristic curve analyses were conducted. Genes associated with DLBCL patient prognosis were additionally identified via WCGNA analyses of the TCGA database. The expression of PLA2G7 in DLBCL patient clinical samples was further assessed, and the functional role of this gene in DLBCL was assessed through in vitro and bioinformatics analyses. Results DLBCL-related DEGs were found to be most closely associated with immune responses, cell proliferation, and angiogenesis. WCGNA analyses revealed that PLA2G7 exhibited prognostic value in DLBCL patients, and the upregulation of this gene in DLBCL patient samples was subsequently validated. PLA2G7 was also found to be closely linked to tumor microenvironmental composition such that DLBCL patients expressing higher levels of this gene exhibited high local monocyte and gamma delta T cell levels. In vitro experiments also revealed that knocking down PLA2G7 expression was sufficient to impair the migration and proliferation of DLBCL cells while promoting their apoptotic death. Furthmore, the specific inhibitor of PLA2G7, darapladib, could noticeably restrained the DLBCL cell viability and induced apoptosis. Conclusions PLA2G7 may represent an important diagnostic, prognostic, or therapeutic biomarker in patients with DLBCL.

First Identification of a Large Set of Serine Hydrolases by Activity-Based Protein Profiling in Dibutyl Phthalate-Exposed Zebrafish Larvae

“…About 70% of human genes have at least one obvious zebrafish orthologue [51]. Identification, in this study, of four SHs human orthologue used as biomarkers in the diagnosis and treatment efficacy of several forms of cancer (PLA2G7, CELA1 and FASN) [52][53][54], dyslipidemia (LCAT) [55] and ischemic stroke (PLA2G7) [56], suggests that zebrafish (larvae) may be a relevant model for the SHs inhibitor discovery process (e.g., drug discovery [35]).…”

Phospholipase PLA2G7 is complementary to GPX4 in mitigating punicic-acid-induced ferroptosis in prostate cancer cells

“…Here, we propose an additional function for PLA2G7, that is to prevent ferroptosis by releasing hydroperoxides from membrane PLs in PCa cells, as supported by the results obtained via our TLC-based enzymatic assays. PLA2G7 has previously been reported as a potent biomarker of PCa, 66 melanoma 67 and diffuse large B cell lymphoma 68 in vitro , in vivo , and in cancer patients. Interestingly, PLA2G7 knockdown reduced cell migration and metastasis 66 , 68 and sensitized ERG-positive PCa cells to oxidative stress.…”

“…PLA2G7 has previously been reported as a potent biomarker of PCa, 66 melanoma 67 and diffuse large B cell lymphoma 68 in vitro , in vivo , and in cancer patients. Interestingly, PLA2G7 knockdown reduced cell migration and metastasis 66 , 68 and sensitized ERG-positive PCa cells to oxidative stress. 69 In addition, high PLA2G7 expression in cancer cells was shown to be a potent marker of cancer cachexia in mice and humans with different tumor types.…”

A diagnostic scoring model of ENKTCL in the nose-Waldeyer’s ring based on logistic regression: Differential diagnosis from DLBCL

“…It has been demonstrated by several retrospective studies that ENKTCL was more invasive and had poorer prognosis than DLBCL with regards to their clinical features. The incidence, treatment options and prognosis differ between ENKTCL and DLBCL in the nose-Waldeyer’s ring ( 5 , 6 ). Currently, the standard treatment for ENKTCL is to use a combination of anthracycline-free chemotherapy and radiotherapy, or chemotherapy alone ( 7 , 8 ), while the most common treatment regimen for DLBCL is R-CHOP (rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone) ( 8 ).…”