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BMC Cancer

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Open Access 01-12-2021 | Diffuse Large B-Cell Lymphoma | Research

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

Authors: Weili Zheng, Qiaochu Lin, Mohammed Awal Issah, Ziyuan Liao, Jianzhen Shen

Published in: BMC Cancer | Issue 1/2021

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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Swerdlow S, Campo E, Pileri S, Harris N, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. https://doi.org/10.1182/blood-2016-01-643569.CrossRefPubMedPubMedCentral

Shree T, Li Q, Glaser S, Brunson A, Maecker H, Haile R, et al. Impaired immune health in survivors of diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(15):1664–75. https://doi.org/10.1200/JCO.19.01937.CrossRefPubMedPubMedCentral

Li M, Chiang Y, Lyssiotis C, Teater M, Hong J, Shen H, et al. Non-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis. Cancer Cell. 2019;35(6):916–931.e919.CrossRefPubMedPubMedCentral

Deng W, Clipson A, Liu H, Huang Y, Dobson R, Wang M, et al. Variable responses of MYC translocation positive lymphoma cell lines to different combinations of novel agents: impact of BCL2 family protein expression. Transl Oncol. 2018;11(5):1147–54. https://doi.org/10.1016/j.tranon.2018.07.007.CrossRefPubMedPubMedCentral

Reddy A, Zhang J, Davis N, Moffitt A, Love C, Waldrop A, et al. Genetic and functional drivers of diffuse large B cell lymphoma. Cell. 2017;171(2):481–494.e415.CrossRefPubMedPubMedCentral

Su W, Niu X, Ji H, Xu Y, Zhong L, Wang S, et al. A novel classification based on B-cell receptor signal gene expression correlates with prognosis in primary breast diffuse large B-cell lymphoma. J Cancer. 2020;11(9):2431–41. https://doi.org/10.7150/jca.39083.CrossRefPubMedPubMedCentral

Shukla A, Tripathi D. Detecting biomarkers from microarray data using distributed correlation based gene selection. Genes Genomics. 2020;42(4):449–65. https://doi.org/10.1007/s13258-020-00916-w.CrossRefPubMed

Sun C, Cheng X, Wang C, Wang X, Xia B, Zhang Y. Gene expression profiles analysis identifies a novel two-gene signature to predict overall survival in diffuse large B-cell lymphoma. Biosci Rep. 2019;3;39(1):BSR20181293. https://doi.org/10.1042/BSR20181293.

Suh K, Sarojini S, Youssif M, Nalley K, Milinovikj N, Elloumi F, et al. Tissue banking, bioinformatics, and electronic medical records: the front-end requirements for personalized medicine. J Oncol. 2013;2013:368751.CrossRefPubMedPubMedCentral

10.

Liu X, Wu J, Zhang D, Bing Z, Tian J, Ni M, et al. Identification of potential key genes associated with the pathogenesis and prognosis of gastric Cancer based on integrated bioinformatics analysis. Front Genet. 2018;9:265. https://doi.org/10.3389/fgene.2018.00265.CrossRefPubMedPubMedCentral

11.

Vainio P, Lehtinen L, Mirtti T, Hilvo M, Seppänen-Laakso T, Virtanen J, et al. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011;2(12):1176–90. https://doi.org/10.18632/oncotarget.397.CrossRefPubMedPubMedCentral

12.

Alinezhad S, Väänänen R, Mattsson J, Li Y, Tallgrén T, Tong Ochoa N, et al. Validation of novel biomarkers for prostate Cancer progression by the combination of bioinformatics. clinical and functional studies. PloS One. 2016;11(5):e0155901. https://doi.org/10.1371/journal.pone.0155901.CrossRefPubMedPubMedCentral

13.

Saenger Y, Magidson J, Liaw B, de Moll E, Harcharik S, Fu Y, et al. Blood mRNA expression profiling predicts survival in patients treated with tremelimumab. Clin Cancer Res. 2014;20(12):3310–8. https://doi.org/10.1158/1078-0432.CCR-13-2906.CrossRefPubMed

14.

Gómez-Abad C, Pisonero H, Blanco-Aparicio C, Roncador G, González-Menchén A, Martinez-Climent J, et al. PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma. Blood. 2011;118(20):5517–27. https://doi.org/10.1182/blood-2011-03-344374.CrossRefPubMed

15.

Dybkær K, Bøgsted M, Falgreen S, Bødker J, Kjeldsen M, Schmitz A, et al. Diffuse large B-cell lymphoma classification system that associates normal B-cell subset phenotypes with prognosis. J Clin Oncol. 2015;33(12):1379–88. https://doi.org/10.1200/JCO.2014.57.7080.CrossRefPubMedPubMedCentral

16.

Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4(1):2612. https://doi.org/10.1038/ncomms3612.CrossRefPubMed

17.

Zhou Y, Chen L, Zhang Y, Hu S, Dong Z, Wu M, et al. Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer. Mol Med. 2019;25(1):47.CrossRefPubMedPubMedCentral

18.

Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30. https://doi.org/10.1093/nar/28.1.27.CrossRefPubMedPubMedCentral

19.

Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019;28(11):1947–51. https://doi.org/10.1002/pro.3715.CrossRefPubMedPubMedCentral

20.

Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021;49(D1):D545–51. https://doi.org/10.1093/nar/gkaa970.CrossRefPubMed

21.

Langfelder P, Horvath S. Fast R Functions for Robust Correlations and Hierarchical Clustering. J Stat Softw. 2012;46(11):i11. https://doi.org/10.18637/jss.v046.i11.

22.

Tang J, Kong D, Cui Q, Wang K, Zhang D, Gong Y, et al. Prognostic genes of breast Cancer identified by gene co-expression network analysis. Front Oncol. 2018;8:374. https://doi.org/10.3389/fonc.2018.00374.CrossRefPubMedPubMedCentral

23.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102. https://doi.org/10.1093/nar/gkx247.CrossRefPubMedPubMedCentral

24.

Luo Y, Zeng G, Wu S. Identification of microenvironment-related prognostic genes in bladder Cancer based on gene expression profile. Front Genet. 2019;10:1187. https://doi.org/10.3389/fgene.2019.01187.CrossRefPubMedPubMedCentral

25.

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7. https://doi.org/10.1038/nmeth.3337.CrossRefPubMedPubMedCentral

26.

Martelli M, Ferreri A, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri S. Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol. 2013;87(2):146–71. https://doi.org/10.1016/j.critrevonc.2012.12.009.CrossRefPubMed

27.

Wang X, Tan Y, Huang Z, Huang N, Gao M, Zhou F, et al. Disrupting myddosome assembly in diffuse large B-cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. Oncol Rep. 2019;42(5):1755–66. https://doi.org/10.3892/or.2019.7282.CrossRefPubMedPubMedCentral

28.

Low H, Png C, Li C, Wang Y, Wong S, Zhang Y. Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness. Oncotarget. 2016;7(34):55473–90. https://doi.org/10.18632/oncotarget.10980.CrossRefPubMedPubMedCentral

29.

Vainio P, Gupta S, Ketola K, Mirtti T, Mpindi J, Kohonen P, et al. Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identified as putative novel therapeutic targets in prostate cancer. Am J Pathol. 2011;178(2):525–36. https://doi.org/10.1016/j.ajpath.2010.10.002.CrossRefPubMedPubMedCentral

30.

Shain K, Dalton W, Tao J. The tumor microenvironment shapes hallmarks of mature B-cell malignancies. Oncogene. 2015;34(36):4673–82. https://doi.org/10.1038/onc.2014.403.CrossRefPubMedPubMedCentral

31.

Kuang Z, Li X, Liu R, Chen S, Tu J. Comprehensive characterization of Cachexia-inducing factors in diffuse large B-cell lymphoma reveals a molecular subtype and a prognosis-related signature. Front Cell Dev Biol. 2021;9:648856. https://doi.org/10.3389/fcell.2021.648856.CrossRefPubMedPubMedCentral

32.

Qiao L, Li H, Zhang Y, Shen D, Liu P, Che Y. CD24 contributes to treatment effect in ABC-DLBCL patients with R-CHOP resistance. Pharmacogenomics Personalized Med. 2021;14:591–9. https://doi.org/10.2147/PGPM.S310816.CrossRef

33.

Noyori O, Komohara Y, Nasser H, Hiyoshi M, Ma C, Pan C, et al. Expression of IL-34 correlates with macrophage infiltration and prognosis of diffuse large B-cell lymphoma. Clin Transl Immunol. 2019;8(8):e1074. https://doi.org/10.1002/cti2.1074.CrossRef

34.

Li Y, Shi Z, Wang X, Gu K, Zhai Z. Tumor-associated macrophages predict prognosis in diffuse large B-cell lymphoma and correlation with peripheral absolute monocyte count. BMC Cancer. 2019;19(1):1049. https://doi.org/10.1186/s12885-019-6208-x.CrossRefPubMedPubMedCentral

Title: Identification of PLA2G7 as a novel biomarker of diffuse large B cell lymphoma
Authors: Weili Zheng
Qiaochu Lin
Mohammed Awal Issah
Ziyuan Liao
Jianzhen Shen
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Biomarkers
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08660-4

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Abstract

Background

Methods

Results

Conclusions

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