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Cited by 21Lymphoma Diagnosis and TreatmentBreast Cancer Treatment StudiesCNS Lymphoma Diagnosis and Treatment

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

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Zheng, Weili, Lin, Qiaochu, Issah, Mohammed Awal, Liao, Ziyuan, Shen, Jianzhen·2021·BMC Cancer
DOI 10.1186/s12885-021-08660-4PMC PMC8369790
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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.

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  • Inhibitors of secretory (varespladib) or lipoprotein-associated (darapladib) PLA2 failed to protect INV cells from IKE-induced ferroptosis within a non-cytotoxic concentration range.

    “By contrast, inhibitors of the secretory (varespladib) or lipoprotein-associated (darapladib) PLA2 used within a concentration range that was not cytotoxic per se (32, 33), failed to do so (fig. S5, B to D).”

    From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [32]

    The Results section identifies darapladib as a PLA2G7 inhibitor and measures its cytotoxicity in DB and SU-DHL-2 lymphoma cells. It does not establish a non-cytotoxic concentration range in INV cells or test whether darapladib or varespladib protects those cells from IKE-induced ferroptosis. The cited paper therefore supports the inhibitor identification, but not the claimed experimental conditions or outcome. (LLM, conf=0.85)

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Authors
Zheng, W., Lin, Q., Issah, M. A., Liao, Z., & Shen, J.
Affiliations
Fujian Medical University (CN)
Corresponding author
Shen, Jianzhen
ORCID
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2021-08-17
Volume
21
Issue
1
Pages
927-927
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/s12885-021-08660-4
PMC
PMC8369790
OpenAlex
W3195275355
Cited by
21
References
35
Citations by year
2026: 2 · 2025: 3 · 2024: 12 · 2023: 3 · 2022: 1
FWCI
2.67
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Fujian Medical University (Min201704, 2020QH2015)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Neurology › CNS Lymphoma Diagnosis and Treatment
Keywords
diffuse large B-cell lymphoma, PLA2G7, prognostic factors, diagnostic biomarkers, differentially expressed genes, tumor microenvironment, monocytes, γδ T cells, darapladib, apoptosis, cell proliferation, cell migration, non-Hodgkin lymphoma
MeSH terms
Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Tumor Cells, Cultured, Biomarkers, Tumor, Survival Rate, Case-Control Studies, Lymphoma, Large B-Cell, Diffuse, Apoptosis, Gene Expression Profiling, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Cell Proliferation, Transcriptome

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